FAM91A1

Chr 8

family with sequence similarity 91 member A1

NCBI Gene: 157769 ENSG00000176853 UniProt: Q658Y4

The protein functions as a component of the WDR11 complex that facilitates golgin-mediated capture of AP-1 generated vesicles at the trans-Golgi network. This gene is highly constrained against loss-of-function variants (LOEUF 0.488), suggesting mutations would likely cause severe disease, though no specific clinical phenotypes have been established in humans yet.

ResearchSummary from RefSeq, UniProt

Involved in intracellular protein transport and vesicle tethering to Golgi. Located in cytoplasmic vesicle and trans-Golgi network. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.49

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.49LOEUF

pLI 0.000

Z-score 4.44

OE 0.32 (0.22–0.49)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.16Z-score

OE missense 0.71 (0.65–0.78)

312 obs / 439.7 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.32 (0.22–0.49)

0≤0.351.4

Missense OE?0.71 (0.65–0.78)

0≤0.61.4

Synonymous OE?0.86

0≤1.21.6

LoF obs/exp: 16 / 49.8Missense obs/exp: 312 / 439.7Syn Z: 1.33

Background carrier burden — how many people carry a rare variant somewhere in FAM91A1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 88

795 rare PASS variants

Rare truncating (LoF)

1 in 2,800

85 rare PASS variants

Rare synonymous (reference)

1 in 90

330 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for FAM91A1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 120	1 in 3,100
South Asian	~43k	1 in 110	1 in 1,500
Remaining (unassigned)	~30k	1 in 71	1 in 6,000
European (Finnish)	~27k	1 in 470	1 in 4,400
Admixed American	~22k	1 in 110	1 in 1,900
African / African American	~21k	1 in 100	1 in 2,100
East Asian	~20k	1 in 73	1 in 2,100
Ashkenazi Jewish	~13k	1 in 1,100	≈ 1 in 3,200
Middle Eastern	~2,884	1 in 99	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 23 of 24 coding exons well covered in gnomAD exomes; exon 10 marginal. Genomes: all 24.? see exons ↓