FAM8A1

Summary

FAM8A1 (family with sequence similarity 8 member A1, HGNC:16372) is a protein-coding gene on chromosome 6p22.3, encoding Protein FAM8A1 (Q9UBU6). Plays a role in the assembly of the HRD1 complex, a complex involved in the ubiquitin-proteasome-dependent process of ER-associated degradation (ERAD).

Predicted to be involved in ERAD pathway. Part of Hrd1p ubiquitin ligase complex.

Source: NCBI Gene 51439 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 64 total
• MANE Select transcript: NM_016255

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16372
Approved symbol	FAM8A1
Name	family with sequence similarity 8 member A1
Location	6p22.3
Locus type	gene with protein product
Status	Approved
Aliases	AHCP
Ensembl gene	ENSG00000137414
Ensembl biotype	protein_coding
OMIM	618409
Entrez	51439

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000259963, ENST00000685064, ENST00000688732, ENST00000689378, ENST00000690940, ENST00000691422, ENST00000692803, ENST00000967813

RefSeq mRNA: 1 — MANE Select: NM_016255 NM_016255

CCDS: CCDS4540

Canonical transcript exons

ENST00000259963 — 5 exons

Exon	Start	End
ENSE00000848130	17600302	17601121
ENSE00000848131	17602590	17602710
ENSE00000848132	17604906	17605029
ENSE00000848133	17605874	17606013
ENSE00000848134	17608195	17611715

Expression profiles

Bgee: expression breadth ubiquitous, 298 present calls, max score 98.37.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.3940 / max 444.6933, expressed in 1804 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
66157	13.6034	1788
66156	2.7906	1299

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 23	UBERON:0013554	98.37	gold quality
middle temporal gyrus	UBERON:0002771	97.66	gold quality
choroid plexus epithelium	UBERON:0003911	97.63	gold quality
parotid gland	UBERON:0001831	96.94	gold quality
endothelial cell	CL:0000115	96.61	gold quality
germinal epithelium of ovary	UBERON:0001304	96.42	gold quality
upper leg skin	UBERON:0004262	96.23	gold quality
bronchial epithelial cell	CL:0002328	96.09	gold quality
seminal vesicle	UBERON:0000998	96.07	gold quality
skin of hip	UBERON:0001554	95.99	gold quality
parietal pleura	UBERON:0002400	95.83	gold quality
lateral nuclear group of thalamus	UBERON:0002736	95.71	gold quality
caput epididymis	UBERON:0004358	95.65	gold quality
nephron tubule	UBERON:0001231	95.63	gold quality
pleura	UBERON:0000977	95.48	gold quality
entorhinal cortex	UBERON:0002728	95.31	gold quality
tibia	UBERON:0000979	95.26	gold quality
lateral globus pallidus	UBERON:0002476	95.25	gold quality
visceral pleura	UBERON:0002401	95.21	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	95.15	gold quality
hair follicle	UBERON:0002073	95.04	gold quality
substantia nigra pars compacta	UBERON:0001965	94.98	gold quality
cauda epididymis	UBERON:0004360	94.87	gold quality
mucosa of paranasal sinus	UBERON:0005030	94.84	gold quality
pigmented layer of retina	UBERON:0001782	94.79	gold quality
retina	UBERON:0000966	94.76	gold quality
epithelium of bronchus	UBERON:0002031	94.71	gold quality
colonic mucosa	UBERON:0000317	94.65	gold quality
mucosa of sigmoid colon	UBERON:0004993	94.61	gold quality
bronchus	UBERON:0002185	94.53	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.62

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

158 targeting FAM8A1, 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-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-3163	100.00	77.23	8605
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-651-3P	99.94	73.48	5177

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	fam8a1b	ENSDARG00000004308
danio_rerio	fam8a1a	ENSDARG00000017111
mus_musculus	Fam8a1	ENSMUSG00000069237
rattus_norvegicus	Fam8a1	ENSRNOG00000026120
drosophila_melanogaster	CG8237	FBGN0033350
caenorhabditis_elegans		WBGENE00018593

Protein

Protein identifiers

Protein FAM8A1 — Q9UBU6 (reviewed: Q9UBU6)

Alternative names: Autosomal highly conserved protein

All UniProt accessions (4): Q9UBU6, A0A8I5KTS2, A0A8I5KV35, B4DK49

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in the assembly of the HRD1 complex, a complex involved in the ubiquitin-proteasome-dependent process of ER-associated degradation (ERAD).

Subunit / interactions. Component of the HRD1 complex, which comprises at least SYNV1/HRD1, FAM8A1, HERPUD1/HERP, OS9, SEL1L and UBE2J1. This interaction stabilizes FAM8A1 protein, preventing its proteasomal degradation. FAM8A1 binding to SYNV1 may promote recruitment of HERPUD1 to the HRD1 complex.

Subcellular location. Membrane.

Tissue specificity. Ubiquitously expressed, with a higher level of expression in testis.

RefSeq proteins (1): NP_057339* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010432	RDD	Domain
IPR039871	FAM8A1	Family

Pfam: PF06271

UniProt features (14 total): transmembrane region 3, compositionally biased region 3, region of interest 3, mutagenesis site 2, chain 1, modified residue 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UBU6-F1	59.45	0.06

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 229

Mutagenesis-validated functional residues (2):

Position	Phenotype
120–122	decreased interaction with syvn1 and herpud1.
131	decreased interaction with herpud1; no effect on interaction with syvn1.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 221 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, GSE45365_NK_CELL_VS_CD8_TCELL_UP, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, MORF_ATRX, GCM_ZNF198, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_UP, SCHLOSSER_SERUM_RESPONSE_DN, GOBP_PROTEASOMAL_PROTEIN_CATABOLIC_PROCESS, GOBP_ERAD_PATHWAY

GO Biological Process (1): ERAD pathway (GO:0036503)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (2): Hrd1p ubiquitin ligase complex (GO:0000836), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
proteasomal protein catabolic process	1
response to endoplasmic reticulum stress	1
response to chemical	1
binding	1
ER ubiquitin ligase complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

664 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FAM8A1	ERLEC1	Q96DZ1	798
FAM8A1	SEL1L	Q9UBV2	750
FAM8A1	OS9	Q13438	729
FAM8A1	UBE2J1	Q9Y385	631
FAM8A1	EMC3	Q9P0I2	594
FAM8A1	ERLIN2	O94905	594
FAM8A1	TMUB1	Q9BVT8	574
FAM8A1	AUP1	Q9Y679	542
FAM8A1	WDR25	Q64LD2	533
FAM8A1	RNF5	Q99942	525
FAM8A1	RNF170	Q96K19	506
FAM8A1	RNF185	Q96GF1	500
FAM8A1	HERPUD2	Q9BSE4	494
FAM8A1	TMUB2	Q71RG4	491
FAM8A1	TMED1	Q13445	490

IntAct

123 interactions, top by confidence:

A	B	Type	Score
SEL1L	OS9	psi-mi:“MI:0914”(association)	0.860
FAM8A1	SYVN1	psi-mi:“MI:0915”(physical association)	0.790
SYVN1	FAM8A1	psi-mi:“MI:0914”(association)	0.790
FAM8A1	SYVN1	psi-mi:“MI:0914”(association)	0.790
FAM8A1	SYVN1	psi-mi:“MI:0403”(colocalization)	0.790
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
SYVN1	OS9	psi-mi:“MI:0914”(association)	0.690
	PMPCB	psi-mi:“MI:0914”(association)	0.640
FUT3	C1QL1	psi-mi:“MI:0914”(association)	0.530
SLC51A	TMEM63A	psi-mi:“MI:0914”(association)	0.530
YIPF3	TMEM120B	psi-mi:“MI:0914”(association)	0.530
WBP1	EXTL3	psi-mi:“MI:0914”(association)	0.530
PTGIR	TMEM63A	psi-mi:“MI:0914”(association)	0.530
VDAC3	HRAS	psi-mi:“MI:0914”(association)	0.530
TMEM9	ESYT2	psi-mi:“MI:0914”(association)	0.530
CREB3	MYO9A	psi-mi:“MI:0914”(association)	0.530
FAM8A1	PLSCR1	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
LY6G6D	HSPA5	psi-mi:“MI:0914”(association)	0.500
SYVN1	HERPUD1	psi-mi:“MI:0914”(association)	0.460

BioGRID (150): FAM8A1 (Affinity Capture-MS), SYVN1 (Affinity Capture-MS), OS9 (Affinity Capture-MS), CAPRIN2 (Affinity Capture-MS), SEL1L (Affinity Capture-MS), ERLEC1 (Affinity Capture-MS), FAM8A1 (Affinity Capture-MS), FAM8A1 (Affinity Capture-Western), FAM8A1 (Affinity Capture-MS), FAM8A1 (Affinity Capture-MS), FAM8A1 (Affinity Capture-MS), FAM8A1 (Affinity Capture-MS), FAM8A1 (Affinity Capture-MS), FAM8A1 (Affinity Capture-MS), FAM8A1 (Affinity Capture-MS)

ESM2 similar proteins: A1YFY1, A2AH22, A2T6X5, A3KPW9, A4IH17, A5D9M6, A7X5R6, E7FAG6, O35445, P46379, Q09463, Q0II22, Q13501, Q15011, Q1W1Y5, Q3KPV4, Q3V209, Q4V9Y1, Q56B11, Q5M807, Q5PRF9, Q5R5B0, Q5RBA5, Q64337, Q6DIP3, Q6MG49, Q6MGB6, Q6P135, Q6PA26, Q6PC78, Q80XS6, Q8BIG4, Q8IZL8, Q8LPN7, Q8WMN5, Q91YL2, Q99942, Q9BV68, Q9C0C7, Q9D0C1

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
FAM8A1	“up-regulates activity”	SYVN1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 136 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Defective CFTR causes cystic fibrosis	6	15.0×	4e-04
Hh mutants are degraded by ERAD	5	13.8×	2e-03
R-HSA-425366	6	12.4×	8e-04
Hedgehog ligand biogenesis	5	12.0×	4e-03
AMPK-induced ERAD and lysosome mediated degradation of PD-L1(CD274)	5	11.0×	5e-03
R-HSA-425393	7	10.3×	6e-04
SLC-mediated transmembrane transport	13	8.7×	1e-06
ABC-family protein mediated transport	6	8.3×	5e-03

GO biological processes:

GO term	Partners	Fold	FDR
retrograde protein transport, ER to cytosol	6	48.8×	6e-07
endoplasmic reticulum unfolded protein response	7	17.0×	4e-05
ERAD pathway	10	14.8×	6e-07
sodium ion transport	5	11.1×	9e-03
response to endoplasmic reticulum stress	6	8.2×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	47
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

475 predictions. Top by Δscore:

Variant	Effect	Δscore
6:17601119:CAGGT:C	donor_loss	1.0000
6:17601120:AG:A	donor_loss	1.0000
6:17601121:GG:G	donor_loss	1.0000
6:17601122:GT:G	donor_loss	1.0000
6:17601123:T:G	donor_loss	1.0000
6:17602585:TACA:T	acceptor_loss	1.0000
6:17602587:CAGG:C	acceptor_loss	1.0000
6:17602588:A:AG	acceptor_gain	1.0000
6:17602588:A:C	acceptor_loss	1.0000
6:17602589:G:GT	acceptor_gain	1.0000
6:17602589:GGC:G	acceptor_gain	1.0000
6:17602589:GGCA:G	acceptor_gain	1.0000
6:17602708:AAAGT:A	donor_loss	1.0000
6:17602710:AG:A	donor_loss	1.0000
6:17602711:G:A	donor_loss	1.0000
6:17602711:G:GG	donor_gain	1.0000
6:17602712:TAAG:T	donor_loss	1.0000
6:17602716:T:G	donor_gain	1.0000
6:17604900:GTGTA:G	acceptor_loss	1.0000
6:17604901:TGTAG:T	acceptor_loss	1.0000
6:17604902:GTAGG:G	acceptor_loss	1.0000
6:17604905:GGGAT:G	acceptor_gain	1.0000
6:17605870:TTA:T	acceptor_loss	1.0000
6:17605871:TA:T	acceptor_loss	1.0000
6:17605872:A:AG	acceptor_gain	1.0000
6:17605873:G:GC	acceptor_loss	1.0000
6:17605873:G:GG	acceptor_gain	1.0000
6:17605873:GAT:G	acceptor_gain	1.0000
6:17605873:GATA:G	acceptor_gain	1.0000
6:17606014:G:GG	donor_gain	1.0000

AlphaMissense

2639 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:17602608:C:A	P244Q	1.000
6:17602623:G:C	R249T	1.000
6:17602623:G:T	R249I	1.000
6:17602624:A:C	R249S	1.000
6:17602624:A:T	R249S	1.000
6:17602634:G:A	E253K	1.000
6:17602635:A:T	E253V	1.000
6:17602636:G:C	E253D	1.000
6:17602636:G:T	E253D	1.000
6:17602643:G:A	D256N	1.000
6:17602643:G:C	D256H	1.000
6:17602643:G:T	D256Y	1.000
6:17602644:A:C	D256A	1.000
6:17602644:A:G	D256G	1.000
6:17602644:A:T	D256V	1.000
6:17602645:T:A	D256E	1.000
6:17602645:T:G	D256E	1.000
6:17602646:T:C	F257L	1.000
6:17602648:C:A	F257L	1.000
6:17602648:C:G	F257L	1.000
6:17602656:T:A	L260H	1.000
6:17602656:T:C	L260P	1.000
6:17602669:A:C	K264N	1.000
6:17602669:A:T	K264N	1.000
6:17604998:T:C	L309P	1.000
6:17605007:G:C	R312T	1.000
6:17605008:A:C	R312S	1.000
6:17605008:A:T	R312S	1.000
6:17605018:T:C	C316R	1.000
6:17605027:G:A	E319K	1.000

dbSNP variants (sampled 300 via entrez): RS1000283608 (6:17607811 G>GT), RS1000358308 (6:17607492 CTA>C), RS1000389030 (6:17599083 C>T), RS1000405870 (6:17604707 C>A,G), RS1000727638 (6:17611476 G>A), RS1000728597 (6:17602830 C>G,T), RS1000740022 (6:17603227 C>T), RS1000904351 (6:17602283 C>G), RS1001207551 (6:17601941 A>G), RS1001430906 (6:17600003 C>T), RS1001630896 (6:17605203 C>G), RS1001723004 (6:17599147 C>T), RS1001780238 (6:17599403 C>T), RS1001893978 (6:17611885 A>C,G), RS1002084663 (6:17605494 C>T)

Disease associations

OMIM: gene MIM:618409 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST005688_15	Idiopathic intracranial hypertension	2.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
perfluorooctane sulfonic acid	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
zinc chromate	increases abundance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	increases abundance, increases expression	1
jinfukang	decreases expression	1
(+)-JQ1 compound	increases expression	1
Decitabine	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Azacitidine	increases expression	1
Caffeine	decreases phosphorylation	1
Curcumin	increases expression	1
Endosulfan	decreases expression	1
Estradiol	affects cotreatment, decreases expression	1
Lead	affects expression	1
Silicon Dioxide	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	affects expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	decreases methylation	1
Aflatoxin M1	decreases expression	1
Lactic Acid	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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