FAM91A1

Summary

FAM91A1 (family with sequence similarity 91 member A1, HGNC:26306) is a protein-coding gene on chromosome 8q24.13, encoding Protein FAM91A1 (Q658Y4). As component of the WDR11 complex acts together with TBC1D23 to facilitate the golgin-mediated capture of vesicles generated using AP-1.

Involved in intracellular protein transport and vesicle tethering to Golgi. Located in cytoplasmic vesicle and trans-Golgi network.

Source: NCBI Gene 157769 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 126 total
• Druggable target: yes
• MANE Select transcript: NM_144963

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26306
Approved symbol	FAM91A1
Name	family with sequence similarity 91 member A1
Location	8q24.13
Locus type	gene with protein product
Status	Approved
Aliases	FLJ23790
Ensembl gene	ENSG00000176853
Ensembl biotype	protein_coding
Entrez	157769

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 8 protein_coding, 3 nonsense_mediated_decay, 3 retained_intron

ENST00000334705, ENST00000517912, ENST00000518333, ENST00000518976, ENST00000519721, ENST00000520246, ENST00000521166, ENST00000521704, ENST00000870918, ENST00000870919, ENST00000870920, ENST00000913291, ENST00000913292, ENST00000913293

RefSeq mRNA: 3 — MANE Select: NM_144963 NM_001317917, NM_001317918, NM_144963

CCDS: CCDS6346, CCDS83322

Canonical transcript exons

ENST00000334705 — 24 exons

Exon	Start	End
ENSE00001476070	123812519	123815452
ENSE00001649660	123777265	123777322
ENSE00001703163	123775147	123775298
ENSE00001728861	123768439	123768774
ENSE00001746886	123779985	123780075
ENSE00001772164	123774080	123774164
ENSE00001795927	123778659	123778772
ENSE00001803098	123778025	123778092
ENSE00003468882	123810282	123810351
ENSE00003510041	123780480	123780542
ENSE00003518842	123805267	123805339
ENSE00003525284	123784470	123784576
ENSE00003529780	123787664	123787750
ENSE00003543699	123799520	123799654
ENSE00003562507	123785081	123785119
ENSE00003580896	123798090	123798238
ENSE00003582571	123785629	123785741
ENSE00003583102	123799772	123799885
ENSE00003669915	123786495	123786610
ENSE00003676972	123808272	123808376
ENSE00003677370	123808893	123809016
ENSE00003678542	123789613	123789745
ENSE00003684933	123806080	123806229
ENSE00003693158	123787261	123787373

Expression profiles

Bgee: expression breadth ubiquitous, 252 present calls, max score 94.99.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 41.6777 / max 504.1870, expressed in 1823 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
90489	41.6777	1823

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	94.99	gold quality
epithelial cell of pancreas	CL:0000083	94.27	gold quality
monocyte	CL:0000576	94.18	gold quality
leukocyte	CL:0000738	93.58	gold quality
islet of Langerhans	UBERON:0000006	92.56	gold quality
adrenal tissue	UBERON:0018303	92.26	gold quality
calcaneal tendon	UBERON:0003701	92.13	gold quality
bone marrow cell	CL:0002092	91.91	gold quality
lower lobe of lung	UBERON:0008949	91.69	gold quality
germinal epithelium of ovary	UBERON:0001304	91.54	gold quality
palpebral conjunctiva	UBERON:0001812	91.19	gold quality
bone marrow	UBERON:0002371	90.91	gold quality
amniotic fluid	UBERON:0000173	90.86	gold quality
upper leg skin	UBERON:0004262	90.82	gold quality
vermiform appendix	UBERON:0001154	90.80	gold quality
rectum	UBERON:0001052	90.61	gold quality
gall bladder	UBERON:0002110	90.43	gold quality
esophagus squamous epithelium	UBERON:0006920	90.40	gold quality
pancreatic ductal cell	CL:0002079	90.35	gold quality
skin of hip	UBERON:0001554	90.34	gold quality
stromal cell of endometrium	CL:0002255	90.06	gold quality
lymph node	UBERON:0000029	89.86	gold quality
mucosa of stomach	UBERON:0001199	89.68	gold quality
right lung	UBERON:0002167	89.67	gold quality
tonsil	UBERON:0002372	89.65	gold quality
smooth muscle tissue	UBERON:0001135	89.54	gold quality
endometrium	UBERON:0001295	89.43	gold quality
caecum	UBERON:0001153	89.42	gold quality
upper arm skin	UBERON:0004263	89.26	gold quality
epithelium of nasopharynx	UBERON:0001951	89.24	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.04

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

173 targeting FAM91A1, 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-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3613-3P	100.00	76.36	7965
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-4668-3P	100.00	68.74	2635
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-9-5P	100.00	72.28	2361
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-LET-7F-2-3P	99.98	70.98	2588

Literature-anchored findings (GeneRIF, showing 1)

• FAM91A1-TBC1D23 complex structure reveals human genetic variations susceptible for PCH. (PMID:37903274)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	fam91a1	ENSDARG00000003320
mus_musculus	Fam91a1	ENSMUSG00000037119
rattus_norvegicus	Fam91a1	ENSRNOG00000008271
drosophila_melanogaster	CG7600	FBGN0064766
caenorhabditis_elegans	F33H2.2	WBGENE00009366

Protein

Protein identifiers

Protein FAM91A1 — Q658Y4 (reviewed: Q658Y4)

All UniProt accessions (5): E7ER68, G3V120, Q658Y4, H0YBR6, H0YC80

UniProt curated annotations — full annotation on UniProt →

Function. As component of the WDR11 complex acts together with TBC1D23 to facilitate the golgin-mediated capture of vesicles generated using AP-1.

Subunit / interactions. Component of the complex WDR11 composed of C17orf75, FAM91A1 and WDR11; FAM91A1 and WDR11 are required for proper location of the complex. Interacts with golgins GOLGA1 and GOLGA4 and with TBC1D23; interaction with golgins may be mediated by TBC1D23 and interaction with TBC1D23 recruits TBC1D23 to AP-1-derived vesicles.

Subcellular location. Golgi apparatus. trans-Golgi network. Cytoplasmic vesicle.

Similarity. Belongs to the FAM91 family.

RefSeq proteins (3): NP_001304846, NP_001304847, NP_659400* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028091	FAM91_N_dom	Domain
IPR028097	FAM91_C_dom	Domain
IPR039199	FAM91	Family

Pfam: PF14647, PF14648

UniProt features (70 total): helix 31, strand 22, turn 6, modified residue 4, region of interest 2, sequence variant 2, compositionally biased region 2, chain 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
8JJ9	X-RAY DIFFRACTION	2.51
8Z9M	ELECTRON MICROSCOPY	3.3
8XFB	ELECTRON MICROSCOPY	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q658Y4-F1	77.89	0.41

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 (4): 332, 340, 671, 828

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9013407	RHOH GTPase cycle

MSigDB gene sets: 213 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, GOBP_VESICLE_LOCALIZATION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, CMYB_01, GOBP_VESICLE_TARGETING, GOBP_VESICLE_MEDIATED_TRANSPORT, CEBPB_01, EVI1_05, GGGCATT_MIR365, GOCC_TRANS_GOLGI_NETWORK, TGCTGAY_UNKNOWN, GATA6_01, WTGAAAT_UNKNOWN

GO Biological Process (2): intracellular protein transport (GO:0006886), obsolete vesicle tethering to Golgi (GO:0099041)

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

GO Cellular Component (3): trans-Golgi network (GO:0005802), cytoplasmic vesicle (GO:0031410), Golgi apparatus (GO:0005794)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
RHO GTPase cycle	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	2
intracellular protein localization	1
protein transport	1
intracellular transport	1
binding	1
Golgi apparatus subcompartment	1
intracellular vesicle	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1134 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FAM91A1	TBC1D23	Q9NUY8	792
FAM91A1	C17orf75	Q9HAS0	788
FAM91A1	TMEM164	Q5U3C3	527
FAM91A1	SNAPIN	O95295	519
FAM91A1	SERTM1	A2A2V5	506
FAM91A1	CPD	O75976	500
FAM91A1	GOLGA4	Q13439	494
FAM91A1	NTAQ1	Q96HA8	490
FAM91A1	BLOC1S6	Q9UL45	490
FAM91A1	RMDN1	Q96DB5	479
FAM91A1	TMEM14A	Q9Y6G1	476
FAM91A1	ANAPC15	P60006	473
FAM91A1	SUGCT	Q9HAC7	449
FAM91A1	KIAA0319L	Q8IZA0	446
FAM91A1	DPRX	A6NFQ7	445

IntAct

110 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:2364”(proximity)	0.900
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
ZNF397	ZNF197	psi-mi:“MI:0914”(association)	0.530
TXNIP	PER1	psi-mi:“MI:0914”(association)	0.530
CXCR4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
RNF19B	PIK3R2	psi-mi:“MI:0914”(association)	0.530
SLC5A5	SLC19A2	psi-mi:“MI:0914”(association)	0.530
HLA-B	LTN1	psi-mi:“MI:0914”(association)	0.530
FAM174A	BLTP3B	psi-mi:“MI:0914”(association)	0.530
C3orf18	SPAG9	psi-mi:“MI:0914”(association)	0.530
LHFPL4	ATP5F1B	psi-mi:“MI:0914”(association)	0.530
C17orf75	FAM91A1	psi-mi:“MI:0914”(association)	0.530
SV2A	EXTL3	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
TNFAIP3	LRRIQ3	psi-mi:“MI:2364”(proximity)	0.420
SDC1	ILVBL	psi-mi:“MI:0915”(physical association)	0.400
Kctd5		psi-mi:“MI:0914”(association)	0.350
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
NUDCD1	TUBAL3	psi-mi:“MI:0914”(association)	0.350
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
SNX21	POLR1G	psi-mi:“MI:0914”(association)	0.350
HLA-B		psi-mi:“MI:0914”(association)	0.350
FGF8	ANKHD1	psi-mi:“MI:0914”(association)	0.350
RNF19B		psi-mi:“MI:0914”(association)	0.350
CHRM4	GEMIN2	psi-mi:“MI:0914”(association)	0.350

BioGRID (188): FAM91A1 (Affinity Capture-MS), FAM91A1 (Affinity Capture-MS), FAM91A1 (Affinity Capture-MS), FAM91A1 (Affinity Capture-MS), FAM91A1 (Affinity Capture-MS), FAM91A1 (Affinity Capture-MS), FAM91A1 (Proximity Label-MS), FAM91A1 (Proximity Label-MS), FAM91A1 (Proximity Label-MS), FAM91A1 (Affinity Capture-MS), FAM91A1 (Affinity Capture-MS), FAM91A1 (Affinity Capture-MS), FAM91A1 (Proximity Label-MS), FAM91A1 (Proximity Label-MS), FAM91A1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4IES7, A0JN62, A0JNW5, A2AAE1, A2AGL3, A2RSJ4, A2RT67, A2RUS2, A2RV80, B0LPN4, B1H2P5, E7F240, E9Q401, O00507, O94967, P30957, P48553, P51593, Q14161, Q2LD37, Q3TLI0, Q3UHE1, Q3UVG3, Q3UX43, Q5F361, Q5M7Q1, Q5RAQ5, Q5ZJK1, Q658Y4, Q68CL5, Q6BDS2, Q6P6Y1, Q6TEP1, Q6VNB8, Q7TMY8, Q7TSG1, Q7Z6Z7, Q8BHY8, Q8CB44, Q8CGF6

Diamond homologs: P0C866, Q3UVG3, Q658Y4, Q6TEP1, Q8T158

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 154 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
Signaling by SCF-KIT	5	13.2×	9e-04
Signaling by BRAF and RAF1 fusions	6	10.9×	7e-04
Macroautophagy	8	9.8×	3e-04
Autophagy	6	9.5×	9e-04
Membrane Trafficking	10	3.9×	3e-03
Vesicle-mediated transport	10	3.7×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
mitophagy	7	17.2×	6e-05
autophagosome assembly	6	10.4×	4e-03
protein transport	13	4.4×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	81
Likely benign	4
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

3284 predictions. Top by Δscore:

Variant	Effect	Δscore
8:123768770:GACAG:G	donor_gain	1.0000
8:123768773:AGGT:A	donor_loss	1.0000
8:123768774:GGT:G	donor_loss	1.0000
8:123768775:G:GC	donor_loss	1.0000
8:123774078:A:AC	acceptor_loss	1.0000
8:123774078:A:AG	acceptor_gain	1.0000
8:123774079:G:GG	acceptor_gain	1.0000
8:123774079:G:T	acceptor_loss	1.0000
8:123774079:GA:G	acceptor_gain	1.0000
8:123774079:GAGT:G	acceptor_gain	1.0000
8:123774079:GAGTC:G	acceptor_gain	1.0000
8:123774161:TTAGG:T	donor_loss	1.0000
8:123774162:TAGGT:T	donor_loss	1.0000
8:123774163:AGGT:A	donor_loss	1.0000
8:123774164:GGTA:G	donor_loss	1.0000
8:123774166:TAA:T	donor_loss	1.0000
8:123775140:T:TA	acceptor_gain	1.0000
8:123775142:T:TA	acceptor_gain	1.0000
8:123775143:GCA:G	acceptor_loss	1.0000
8:123775144:CA:C	acceptor_loss	1.0000
8:123775145:A:AG	acceptor_gain	1.0000
8:123775145:AGT:A	acceptor_loss	1.0000
8:123775146:G:GG	acceptor_gain	1.0000
8:123775146:GT:G	acceptor_gain	1.0000
8:123775146:GTT:G	acceptor_gain	1.0000
8:123775146:GTTA:G	acceptor_gain	1.0000
8:123775146:GTTAA:G	acceptor_gain	1.0000
8:123775249:TGA:T	donor_gain	1.0000
8:123775255:GCT:G	donor_gain	1.0000
8:123775295:GGAG:G	donor_gain	1.0000

AlphaMissense

5491 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:123768745:T:A	W15R	1.000
8:123768745:T:C	W15R	1.000
8:123774128:A:C	S41R	1.000
8:123774130:T:A	S41R	1.000
8:123774130:T:G	S41R	1.000
8:123775147:T:A	V53D	1.000
8:123775189:T:C	L67P	1.000
8:123775221:T:G	Y78D	1.000
8:123775225:C:A	P79H	1.000
8:123775234:T:C	L82P	1.000
8:123777286:A:C	S111R	1.000
8:123777288:T:A	S111R	1.000
8:123777288:T:G	S111R	1.000
8:123777289:T:A	Y112N	1.000
8:123777289:T:C	Y112H	1.000
8:123777289:T:G	Y112D	1.000
8:123777290:A:G	Y112C	1.000
8:123777292:G:A	D113N	1.000
8:123777292:G:C	D113H	1.000
8:123777292:G:T	D113Y	1.000
8:123777293:A:C	D113A	1.000
8:123777293:A:G	D113G	1.000
8:123777293:A:T	D113V	1.000
8:123777294:T:A	D113E	1.000
8:123777294:T:G	D113E	1.000
8:123777295:T:C	S114P	1.000
8:123777299:T:C	L115S	1.000
8:123777299:T:G	L115W	1.000
8:123777301:C:A	P116T	1.000
8:123777301:C:T	P116S	1.000

dbSNP variants (sampled 300 via entrez): RS1000056789 (8:123789965 A>G), RS1000099054 (8:123803875 A>G), RS1000225854 (8:123784305 C>T), RS1000274495 (8:123791785 A>G), RS1000355926 (8:123766579 C>G), RS1000364050 (8:123791290 T>A,C), RS1000554478 (8:123804197 G>A), RS1000696140 (8:123811164 A>G,T), RS1000894710 (8:123803849 C>G), RS1000915429 (8:123811398 G>A), RS1000950756 (8:123810922 T>C), RS1000953572 (8:123767020 T>G), RS1001003619 (8:123779363 G>T), RS1001060619 (8:123772688 C>A,T), RS1001351372 (8:123810212 A>C)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST000477_22	Cognitive performance	4.000000e-07
GCST000745_4	Pancreatic cancer	4.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0003926	neuropsychological test

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5465320 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

38 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
Smoke	decreases expression, increases abundance	2
Tobacco Smoke Pollution	increases expression	2
Valproic Acid	decreases methylation, increases expression	2
GSK-J4	increases expression	1
dicrotophos	decreases expression	1
bisphenol A	decreases expression	1
decabromobiphenyl ether	decreases expression	1
trichostatin A	affects expression	1
arsenite	affects binding, decreases reaction	1
methylparaben	increases expression	1
tetrabromobisphenol A	decreases expression	1
coumarin	increases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	increases expression	1
ICG 001	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	affects cotreatment, decreases expression	1
jinfukang	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Air Pollutants	increases abundance, decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Caffeine	decreases phosphorylation	1
Dexamethasone	affects cotreatment, decreases expression	1
Doxorubicin	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5338462	Binding	Binding affinity to Fam91a1 (unknown origin) assessed as fold change in protein upregulation at 200 uM preincubated for 2 hrs followed by pronase addition and measured after 30 mins by coomassie blue staining based SDS-PAGE gel analysis	Structurally Diverse Alkaloids with Anti-Renal-Fibrosis Activity from the Centipede Scolopendra subspinipes mutilans. — J Nat Prod

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_SM96	HAP1 FAM91A1 (-) 1	Cancer cell line	Male
CVCL_SM97	HAP1 FAM91A1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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