FAM167A

Chr 8

family with sequence similarity 167 member A

Also known as: C8orf13, D8S265, DIORA-1

NCBI Gene: 83648 ENSG00000154319 UniProt: Q96KS9

FAM167A encodes a protein of unknown function that localizes to the endoplasmic reticulum. Biallelic mutations cause autosomal recessive developmental and epileptic encephalopathy with severe intellectual disability and early-onset seizures. The gene shows very low constraint against loss-of-function variants, consistent with a recessive inheritance pattern.

Research

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.97

LOEUF

GOF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.97LOEUF

pLI 0.000

Z-score -2.38

OE 2.01 (1.15–1.97)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-1.72Z-score

OE missense 1.42 (1.26–1.60)

192 obs / 135.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?2.01 (1.15–1.97)

0≤0.351.4

Missense OE?1.42 (1.26–1.60)

0≤0.61.4

Synonymous OE?1.55

0≤1.21.6

LoF obs/exp: 13 / 6.5Missense obs/exp: 192 / 135.5Syn Z: -3.31

Background carrier burden — how many people carry a rare variant somewhere in FAM167A?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 130

432 rare PASS variants

Rare truncating (LoF)

1 in 2,400

65 rare PASS variants

Rare synonymous (reference)

1 in 260

187 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for FAM167A. 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 220	1 in 2,600
South Asian	~43k	1 in 90	1 in 2,500
Remaining (unassigned)	~30k	1 in 120	1 in 3,000
European (Finnish)	~27k	1 in 290	≈ 1 in 26,000
Admixed American	~22k	1 in 150	1 in 1,700
African / African American	~21k	1 in 80	1 in 2,800
East Asian	~20k	1 in 86	1 in 3,300
Ashkenazi Jewish	~13k	1 in 810	1 in 2,600
Middle Eastern	~2,884	1 in 170	none seen

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): All 2 coding exons well covered in gnomAD exomes and genomes.? see exons ↓