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The family with sequence similarity 43 member A (FAM43A) gene, also known as; GCO3P195887, GC03P194406, GC03P191784,[5] and NM_153690.3,[6] codes for a 423 bp protein that is conserved in primates, and orthologs have been found in vertebrate and invertebrate species.[7] Three transcripts have been identified, two protein coding isoforms (aAug10, bAug10), and a non-coding transcript (cAug10).[8] Molecular weight of 45.8 kdal in the unphosphorylated state and isoelectric point of 6.1.[9]

AliasesFAM43A, family with sequence similarity 43 member A
External IDsMGI: 2676309 HomoloGene: 17800 GeneCards: FAM43A
Gene location (Human)
Chromosome 3 (human)
Chr.Chromosome 3 (human)[1]
Chromosome 3 (human)
Genomic location for FAM43A
Genomic location for FAM43A
Band3q29Start194,686,544 bp[1]
End194,689,037 bp[1]
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC)Chr 3: 194.69 – 194.69 MbChr 16: 30.6 – 30.6 Mb
PubMed search[3][4]
View/Edit HumanView/Edit Mouse



Located on the long arm of Chromosome 3 at 3q29, FAM43A consists of 2,493 bases; and the translated protein contains a phosphotyrosine interaction domain, putative phosphoinositide binding site and putative peptide binding sites.[10]


The FAM43A gene has been identified in cDNA screening as a possible cancer development and progression candidate gene.[11] Unpublished data from Zhang et al. indicates that FAM43A could possess tumor suppressor function[12] however the direct interaction is unknown. As well as playing a role in cancer development, FAM43A has been identified as a possible autism spectrum disorder (ASD) candidate gene, with mutations within the upstream single nucleotide polymorphism (SNP) rs789859 correlating with the presentation of ASD and learning disorder; suggesting that this SNP is the promoter region for the downstream FAM43A gene.[13] The 2014 study completed by Baron-Cohen et al. involved the screening of 906 K SNPs within the genome to identify possible candidate genes, with FAM43A being the closest gene to the polymorphism.


FAM43A and paralog FAM43B comprise a specific gene family, and share structural homology with the low-density lipoprotein receptor adaptor protein (LDLrP).[14][15] Orthologs were identified in Mammalia, Aves, Actinopterygii, Reptilia, Hemichordata, Cephalochardata, Mollusca, Brachiopoda, Nematoda, and Arthropoda. No orthologs were identified beyond invertebrate species.[16]

Unrooted Phylogenetic tree indicating orthologs in Mammalia, Aves, Actinoptergii, Reptilia, and several invertebrate species.


FAM43A and paralog FAM43B comprise a specific gene family who share structural homology with the low-density lipoprotein receptor adaptor protein (LDLrP).[17]


Scientific Name Name Accession Sequence Similarity %
Gorilla gorilla gorilla XP_004038285.1 99
Orcinus orca killer whale XP_004278817.1 94
Gallus gallus chicken XP_426700.2 74
Danio rerio zebrafish NP_999870.1 71
Python bivittatus python XP_007440325.1 51
Branchiostoma belcheri lancelet XP_0196466582.1 49
Limulus polyphpemus horseshoe crab XP_013779827.1 38
Caenorhabditis elegans nematode NP_509937.1 35

A distant homolog was identified using NCBI protein BLAST, low density lipoprotein receptor adaptor protein 1-like in [Cryptotermes secundus]. However, when the sequence LOC111863195 was compared to Homo sapiens, it was discovered that the homolog mapped to chromosome 1, making it an ortholog of the paralog FAM43B. The fact that FAM43A protein cannot be traced back any further in evolutionary history than invertebrates indicates that this could be the point that FAM43A and paralog FAM43B diverged, approximately 797 million years ago (MYA).


Tissue specific expressionEdit

FAM43A protein is highly expressed in the mouth, vascular system, spleen and ear. Significant expression noted in the adipose tissue, umbilical cord, and bone, with highest expression in the infant developmental stage.[18]

Disease state expressionEdit

Expression is upregulated in head and neck tumor and bladder carcinoma, suggesting an oncogenic function.[19] FAM43A expression is upregulated in Early T-cell precursor (ETP) acute lymphoblastic leukemia (ALL) (GDS4299) and triple negative breast cancer (TNBC) cell lines Hs578T (GDS4092).[20] FAM43A expression map of Mus musculus brain indicated differential expression in the cortex, corpus callosum, and hypothalamus.[21] The primary function of the corpus callosum is to innervate and connect the two hemispheres of the brain. The corpus callosum integrates motor, sensory, and cognitive performance between the cortical region in one hemisphere with its target in the other hemisphere.[22] The hypothalamus links the nervous system to the endocrine system through the pituitary gland.


3q29 microdeletion syndrome (monosomy 3q29) is caused by interstitial deletions of 3q29, mediated by nonallelic homologous recombination between low-copy repeats resulting in a common deletion.[23] 3q29 microdeletion syndrome is marked by the loss of 1.6 million base pairs, including 5 known genes and 17 unknown transcripts. Genes phosphate and cytidyltransferase 1, choline alpha (PYT1A), P21 (RAC1) activated kinase 2 (PAK2), melanotransferrin (MFI2), discs large MAGUK scaffold protein 1 (DLG1), and 3-hydroxybutyrate dehydrogenase 1 (BDH1) have been confirmed and another 7 genes have been implicated with incomplete cDNAs, and the remaining hypothetical genes are yet to be confirmed experimentally.[24] Presentation of 3q29 microdeletion syndrome has shown increased risk for schizophrenia. Gene neighbors PAK2 and DLG1 have been implicated due to interaction with neuroligin and the AMPA receptor subunit GluR1.[25] In 2015, Guida et al identified a novel mutation proximal to the 3q29 microdeletion region that correlated with presentation of oculo auriculo vertebral spectrum (OAVS).[26] Research of Robertson et al. revealed the presence of FAM43A mRNA in the fetal cochlea and association with development of normal hearing function.[27] These findings indicate that variation in FAM43A could be responsible for the development of OAVS.


Transcription factor binding can be seen below within the FAM43A promoter region,[28] searches were completed on the 500 bp preceding the start codon.

Candidate transcription factors and binding sites of FAM43A identified by Genomatix
Matrix Family Detailed Family Information Anchor position Strand Matrix sim. Sequence
ZICF ZIC-family, zinc finger of the cerebellum 1912 - 0.931 cggcgCAGCtgggcg
NEUR NeuroD, Beta2, HLH domain 1912 + 0.985 cgcccaGCTGcgccg
PLAG Pleomorphic adenoma gene 1919 - 0.931 ggaggGCGCcccggcgcagctgg
EGRF EGR/nerve growth factor induced protein C & related factors 1896 - 0.919 ggcggcggCGGCggagcgc
KLFS kruppel like transcription factors 1796 - 0.941 tagggagttGGGGggaggg
GCMF Chorion-specific transcription factors with a GCM DNA binding domain 1742 - 0.919 attaCCCGcacctc
SORY SOX/SORY sex/testes determining and related HMG box factors 1741 + 0.953 agagAATTtacccgcacctcctg
EBOX E-box binding factors 1674 + 0.921 gtgcgcgCGTGtctccc
E2FF E2F-myc activator/cell cycle regulator 1549 + 0.905 tgtgtGCGCgcgtgtct
MTF1 Metal induced transcription factor 1635 + 0.900 ctttGCTCtcgccct
ETSF Human and murine ETS1 factors 1565 - 0.934 aaatgtcaGGAAaaaagctag
FKHD Forkhead domain factors 1541 - 0.986 cgcgtgcAAATaaagag
INSN Insulinoma associated factors 1462 + 0.926 tgttaGGGGaccc

3' untranslated regionEdit

MicroRNA binding sites were identified[29] and then compared to species conservation of FAM43A to determine likely 3' untranslated region (UTR) stem loop structures as depicted to the right.

3' untranslated region secondary structure

Post-translational ModificationEdit

FAM43 is predicted to be a nuclear protein, to identify function, structure and function for LDL receptor adaptor protein (LDLrP) was completed.[30] Conserved residues Y52 and S93 are highlighted in the structure of LDLrP to the right. Three phosphorylation sites were identified with conservation between human and mouse genotypes[31] at T112-p, S114-p, and T-379-p. The translated protein contains a primary and secondary nuclear localization signal and has a predicted GPI-linkage site at D407,[32] and a Caspase 3 and 7 cleavage site from amino acids 404-408[33] indicating possible translocation from the cell membrane to the nucleus.

LDLrP phosphotyrosine interaction domain with Y52 and S93 highlighted.

Interacting ProteinsEdit

Direct interaction with SRPK2 (SRSF Protein Kinase 2), Serine/arginine-rich protein-specific kinase, which phosphorylates substrates at serine residues rich in Arginine/Serine dipeptides (RS domains), involved in the phosphorylation of SR splicing factors and the regulation of splicing. SRSF protein kinase 2 promotes neural apoptosis by up-regulating cyclin-D1 expression through the suppression of p53/TP53 phosphorylation.[34] Protein phosphatase 2A is one of the four major Ser/Thr phosphatases which regulate negative control of cell growth and division.[35] FAM43A shows predicted interaction with the Abelson (ABL) kinase, and ABL members link diverse extracellular stimuli to signaling pathways controlling cell growth, survival, invasion, adhesion, and migration.[36]

Interacting protein alias Full name Function Interaction Type
SRPK2 Serine/arginine-rich protein-specific kinase Phosphorylates substrates at RS domains direct interaction
PPP2R5C Protein Phosphatase 2A Regulatory Subunit B'Gamma Phosphatase 2A regulatory subunit B family physical association
PPP2R1B Protein Phosphatase 2A Scaffold Subunit A beta constant regulatory subunit of protein phosphatase 2 physical association
PPP2R5D Protein Phosphatase 2A Regulatory Subunit B'Delta Phosphatase 2A regulatory subunit B family physical association
PPP2R5A Protein Phosphatase 2A Regulatory Subunit B'Alpha Phosphatase 2A regulatory subunit B family physical association
PPP2R5B Protein Phosphatase 2A Regulatory Subunit B'Beta Phosphatase 2A regulatory subunit B family physical association
PPP2R5E Protein Phosphatase 2A Regulatory Subunit B'Epsilon Phosphastase 2A regulatory subunit B family physical association
SNX6 Sorting Nexin 6 Members contain a phox (PX) phosphoinositide binding domain (intracellular trafficking) physical association


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