FAM81A

Summary

FAM81A (family with sequence similarity 81 member A, HGNC:28379) is a protein-coding gene on chromosome 15q22.2, encoding Protein FAM81A (Q8TBF8). Facilitates the interaction and assembly of proteins within the postsynaptic density by promoting the condensation of postsynaptic proteins via liquid-liquid phase separation.

Predicted to enable molecular condensate scaffold activity. Located in cytoplasm.

Source: NCBI Gene 145773 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 37 total
• MANE Select transcript: NM_152450

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28379
Approved symbol	FAM81A
Name	family with sequence similarity 81 member A
Location	15q22.2
Locus type	gene with protein product
Status	Approved
Aliases	MGC26690
Ensembl gene	ENSG00000157470
Ensembl biotype	protein_coding
OMIM	621329
Entrez	145773

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 17 protein_coding, 3 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000288228, ENST00000557895, ENST00000557914, ENST00000558348, ENST00000558513, ENST00000558900, ENST00000559628, ENST00000560022, ENST00000560074, ENST00000560087, ENST00000560118, ENST00000560123, ENST00000560394, ENST00000560474, ENST00000561361, ENST00000867392, ENST00000867393, ENST00000867394, ENST00000867395, ENST00000943843, ENST00000943844, ENST00000943845

RefSeq mRNA: 1 — MANE Select: NM_152450 NM_152450

CCDS: CCDS45269

Canonical transcript exons

ENST00000288228 — 9 exons

Exon	Start	End
ENSE00001032776	59459933	59460206
ENSE00001032782	59516645	59516840
ENSE00001032787	59507213	59507342
ENSE00001032798	59508863	59508969
ENSE00001032799	59514289	59514424
ENSE00001183483	59438186	59438282
ENSE00001317132	59521254	59523555
ENSE00003463204	59458550	59458646
ENSE00003791414	59492271	59492389

Expression profiles

Bgee: expression breadth ubiquitous, 168 present calls, max score 94.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.0952 / max 244.0114, expressed in 977 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
146984	3.9819	725
146977	0.4479	226
146983	0.1975	82
146981	0.1912	77
146976	0.1865	84
146982	0.0796	39
146985	0.0107	2

Top tissues by expression

256 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	94.65	gold quality
Brodmann (1909) area 9	UBERON:0013540	90.15	gold quality
prefrontal cortex	UBERON:0000451	89.67	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	88.85	gold quality
anterior cingulate cortex	UBERON:0009835	88.85	gold quality
middle temporal gyrus	UBERON:0002771	88.64	gold quality
right frontal lobe	UBERON:0002810	87.62	gold quality
primary visual cortex	UBERON:0002436	87.48	gold quality
neocortex	UBERON:0001950	87.26	gold quality
frontal cortex	UBERON:0001870	86.95	gold quality
cerebral cortex	UBERON:0000956	85.39	gold quality
Brodmann (1909) area 23	UBERON:0013554	85.15	gold quality
right uterine tube	UBERON:0001302	84.27	gold quality
rectum	UBERON:0001052	83.16	gold quality
endothelial cell	CL:0000115	82.81	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.50	gold quality
amygdala	UBERON:0001876	81.91	gold quality
superior frontal gyrus	UBERON:0002661	81.74	gold quality
occipital lobe	UBERON:0002021	81.24	gold quality
forebrain	UBERON:0001890	80.89	gold quality
Ammon’s horn	UBERON:0001954	80.55	gold quality
mucosa of transverse colon	UBERON:0004991	80.41	gold quality
tibial nerve	UBERON:0001323	80.05	gold quality
temporal lobe	UBERON:0001871	79.10	gold quality
postcentral gyrus	UBERON:0002581	78.30	gold quality
nucleus accumbens	UBERON:0001882	78.02	gold quality
hypothalamus	UBERON:0001898	77.91	gold quality
metanephros cortex	UBERON:0010533	77.86	gold quality
caudate nucleus	UBERON:0001873	77.84	gold quality
adenohypophysis	UBERON:0002196	77.80	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.23

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

154 targeting FAM81A, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345

Literature-anchored findings (GeneRIF, showing 1)

• FAM81A identified as a stemness-related gene by screening DNA methylation sites based on machine learning-accessed stemness in pancreatic cancer. (PMID:35574683)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Fam81a	ENSMUSG00000032224
rattus_norvegicus	Fam81a	ENSRNOG00000057501

Paralogs (1): FAM81B (ENSG00000153347)

Protein

Protein identifiers

Protein FAM81A — Q8TBF8 (reviewed: Q8TBF8)

All UniProt accessions (9): Q8TBF8, H0YKL6, H0YKQ6, H0YKW2, H0YLQ5, H0YMF2, H0YMX7, H0YN47, H0YN94

UniProt curated annotations — full annotation on UniProt →

Function. Facilitates the interaction and assembly of proteins within the postsynaptic density by promoting the condensation of postsynaptic proteins via liquid-liquid phase separation. Required for neuronal activity. Accumulation at the postsynaptic density results in enlargement of dendritic spines.

Subunit / interactions. Interacts with DLG4/PSD-95, GRIN2B/GLUN2B and SYNGAP1; the interactions facilitate condensate formation.

Subcellular location. Postsynaptic density. Cytoplasm.

Similarity. Belongs to the FAM81 family.

RefSeq proteins (1): NP_689663* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029619	FAM81	Family

UniProt features (5 total): coiled-coil region 3, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TBF8-F1	82.30	0.54

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 142 (showing top): BENPORATH_ES_WITH_H3K27ME3, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, TGACCTY_ERR1_Q2, NKX61_01, GTGCCTT_MIR506, AP1_Q4_01, TGANTCA_AP1_C, PU1_Q6, AACTTT_UNKNOWN, RGAGGAARY_PU1_Q6, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, TGACCTTG_SF1_Q6, TGGAAA_NFAT_Q4_01, GOCC_POSTSYNAPSE, GAVIN_FOXP3_TARGETS_CLUSTER_P3

GO Biological Process (0):

GO Molecular Function (2): molecular condensate scaffold activity (GO:0140693), protein binding (GO:0005515)

GO Cellular Component (5): cytoplasm (GO:0005737), postsynaptic density (GO:0014069), glutamatergic synapse (GO:0098978), postsynaptic density, intracellular component (GO:0099092), synapse (GO:0045202)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein-macromolecule adaptor activity	1
binding	1
intracellular anatomical structure	1
cellular anatomical structure	1
asymmetric synapse	1
postsynaptic specialization	1
synapse	1
postsynaptic density	1
postsynaptic specialization, intracellular component	1
cell junction	1

Protein interactions and networks

STRING

454 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FAM81A	PTPN20	Q4JDL3	531
FAM81A	C9orf153	Q5TBE3	507
FAM81A	LMBR1L	Q6UX01	503
FAM81A	FBXW10B	O95170	472
FAM81A	GPR171	O14626	463
FAM81A	TOR2A	Q5JU69	463
FAM81A	TMEM179	Q6ZVK1	451
FAM81A	FAM135A	Q9P2D6	442
FAM81A	TMEM145	Q8NBT3	440
FAM81A	TMEM278	A6NKF7	439
FAM81A	SBK2	P0C263	437
FAM81A	ENTREP2	O60320	432
FAM81A	LUZP2	Q86TE4	415
FAM81A	TMED6	Q8WW62	414
FAM81A	FAM171B	Q6P995	401

IntAct

28 interactions, top by confidence:

A	B	Type	Score
NAP1L2	FAM81A	psi-mi:“MI:0915”(physical association)	0.560
PCM1	FAM81A	psi-mi:“MI:0915”(physical association)	0.560
FAM81A	TFIP11	psi-mi:“MI:0915”(physical association)	0.560
STX1B	FAM81A	psi-mi:“MI:0915”(physical association)	0.560
TXLNA	FAM81A	psi-mi:“MI:0915”(physical association)	0.560
FAM81A	RCOR3	psi-mi:“MI:0915”(physical association)	0.560
FAM81A	NAP1L2	psi-mi:“MI:0915”(physical association)	0.560
ZNF655	FAM81A	psi-mi:“MI:0915”(physical association)	0.560
FAM81A	PCCA	psi-mi:“MI:0914”(association)	0.530
FAM81A	ZZEF1	psi-mi:“MI:0914”(association)	0.350
OR52B2	PCCA	psi-mi:“MI:0914”(association)	0.350
OR5C1	PTX3	psi-mi:“MI:0914”(association)	0.350
FAM81A	PCM1	psi-mi:“MI:0915”(physical association)	0.000
FAM81A	TFIP11	psi-mi:“MI:0915”(physical association)	0.000
STX1B	FAM81A	psi-mi:“MI:0915”(physical association)	0.000
TXLNA	FAM81A	psi-mi:“MI:0915”(physical association)	0.000
RCOR3	FAM81A	psi-mi:“MI:0915”(physical association)	0.000
FAM81A	ZNF655	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (21): FAM81A (Affinity Capture-MS), FAM81A (Affinity Capture-MS), FAM81A (Two-hybrid), FAM81A (Two-hybrid), FAM81A (Two-hybrid), FAM81A (Two-hybrid), FAM81A (Two-hybrid), NAP1L2 (Two-hybrid), ZNF655 (Two-hybrid), FAM81A (Affinity Capture-MS), FBXO28 (Affinity Capture-MS), BEND3 (Affinity Capture-MS), ZZEF1 (Affinity Capture-MS), PCCA (Affinity Capture-MS), DSCC1 (Affinity Capture-MS)

ESM2 similar proteins: A2BDR7, A3KGV1, B6MFW3, D4A7T8, F1MA98, F1QC17, F6ZDS4, G5E861, O15078, O35550, O35551, P12270, P61584, P85001, P85120, Q0II90, Q0VFN8, Q15276, Q39618, Q3TDD9, Q3UXZ6, Q3V6T2, Q498G2, Q5BJF6, Q5EE04, Q5TZ80, Q5ZJ27, Q5ZKK5, Q5ZL12, Q66GS9, Q66KE8, Q6A078, Q6AYX5, Q6DFC2, Q6IR70, Q6NRB0, Q6NRC9, Q6NRG6, Q6P5D4, Q6ZMI0

Diamond homologs: D4A7T8, Q0II90, Q3UXZ6, Q8TBF8, Q96LP2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

37 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	25
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1882 predictions. Top by Δscore:

Variant	Effect	Δscore
15:59438279:GCCG:G	donor_gain	1.0000
15:59438280:CCGGT:C	donor_loss	1.0000
15:59438281:CGGTG:C	donor_loss	1.0000
15:59438282:GGTG:G	donor_loss	1.0000
15:59438283:G:GG	donor_gain	1.0000
15:59438283:GTGA:G	donor_loss	1.0000
15:59438284:T:A	donor_loss	1.0000
15:59458544:CAACA:C	acceptor_loss	1.0000
15:59458545:AACAG:A	acceptor_loss	1.0000
15:59458546:ACAG:A	acceptor_loss	1.0000
15:59458547:CA:C	acceptor_loss	1.0000
15:59458548:A:AG	acceptor_gain	1.0000
15:59458548:A:C	acceptor_loss	1.0000
15:59458549:G:GG	acceptor_gain	1.0000
15:59458549:GA:G	acceptor_gain	1.0000
15:59458549:GAT:G	acceptor_gain	1.0000
15:59458549:GATGT:G	acceptor_gain	1.0000
15:59459931:A:AC	acceptor_loss	1.0000
15:59459931:A:AG	acceptor_gain	1.0000
15:59459931:AG:A	acceptor_gain	1.0000
15:59459932:G:A	acceptor_loss	1.0000
15:59459932:G:GA	acceptor_gain	1.0000
15:59459932:GG:G	acceptor_gain	1.0000
15:59459932:GGC:G	acceptor_gain	1.0000
15:59459932:GGCGA:G	acceptor_gain	1.0000
15:59492266:CCCA:C	acceptor_loss	1.0000
15:59492267:CCAG:C	acceptor_loss	1.0000
15:59492268:CA:C	acceptor_loss	1.0000
15:59492387:AAGG:A	donor_loss	1.0000
15:59492390:G:GG	donor_gain	1.0000

AlphaMissense

2460 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:59460052:T:C	L47P	1.000
15:59460063:G:C	A51P	1.000
15:59460064:C:A	A51D	1.000
15:59460157:A:C	H82P	1.000
15:59460169:T:A	I86K	1.000
15:59460190:T:C	L93P	1.000
15:59492275:T:C	L100P	1.000
15:59492371:T:C	L132P	1.000
15:59492381:A:C	R135S	1.000
15:59492381:A:T	R135S	1.000
15:59460052:T:A	L47H	0.999
15:59460076:A:T	K55I	0.999
15:59460077:A:C	K55N	0.999
15:59460077:A:T	K55N	0.999
15:59460148:T:C	L79S	0.999
15:59460156:C:G	H82D	0.999
15:59460169:T:G	I86R	0.999
15:59460174:G:C	A88P	0.999
15:59460178:T:A	I89K	0.999
15:59460181:T:A	V90E	0.999
15:59492296:G:C	R107P	0.999
15:59492298:G:C	D108H	0.999
15:59492299:A:C	D108A	0.999
15:59492299:A:T	D108V	0.999
15:59492367:G:C	D131H	0.999
15:59492371:T:A	L132H	0.999
15:59492376:G:A	G134R	0.999
15:59492376:G:C	G134R	0.999
15:59492379:A:G	R135G	0.999
15:59492380:G:C	R135T	0.999

dbSNP variants (sampled 300 via entrez): RS1000008030 (15:59460277 C>T), RS1000046344 (15:59523706 C>T), RS1000084667 (15:59471549 A>G), RS1000097258 (15:59452255 A>G), RS1000129140 (15:59397543 A>G), RS1000129653 (15:59452057 C>G), RS1000192455 (15:59497913 A>G), RS1000227181 (15:59499962 C>T), RS1000333908 (15:59503176 C>T), RS1000369574 (15:59446865 T>G), RS1000374209 (15:59518808 A>T), RS1000388538 (15:59468401 A>T), RS1000443682 (15:59462552 A>G), RS1000521382 (15:59400610 A>C,T), RS1000525586 (15:59474238 G>A)

Disease associations

OMIM: gene MIM:621329 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): CIC-rearranged sarcoma (MONDO:0956989)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001523_25	Visceral adipose tissue adjusted for BMI	7.000000e-06
GCST009391_1398	Metabolite levels	2.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0010369	lysophosphatidylethanolamine 18:2 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	3
sodium arsenite	decreases expression, increases expression	2
bisphenol A	affects cotreatment, increases methylation	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	increases expression	1
nickel sulfate	increases expression	1
pentanal	increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
jinfukang	increases expression	1
NSC 689534	affects binding, decreases expression	1
Temozolomide	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Air Pollutants	increases expression, increases abundance	1
Amiodarone	increases expression	1
Calcitriol	decreases expression, affects cotreatment	1
Copper	affects binding, decreases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Smoke	increases abundance, increases expression	1
Testosterone	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Triclosan	decreases expression	1
Vincristine	decreases expression	1
Aflatoxin B1	decreases methylation	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

3 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT02389244	PHASE2	ACTIVE_NOT_RECRUITING	A Phase II Study Evaluating Efficacy and Safety of Regorafenib in Patients With Metastatic Bone Sarcomas
NCT06414434	PHASE1	ACTIVE_NOT_RECRUITING	BTX-A51 in Patients With Liposarcoma or CIC-rearranged Sarcoma
NCT06820957	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Testing a New Combination of Anti-cancer Drugs in Patients Newly Diagnosed With Ewing Sarcoma Who Have Cancer That Has Spread to Other Parts of the Body