FAM174B

Chr 15

family with sequence similarity 174 member B

NCBI Gene: 400451 ENSG00000185442 UniProt: Q3ZCQ3

The protein is essential for Golgi structural integrity and involved in Golgi organization. Mutations cause autosomal recessive developmental and epileptic encephalopathy with microcephaly, characterized by early-onset seizures, severe developmental delay, and progressive microcephaly. This gene shows low constraint to loss-of-function variation in the general population.

ResearchSummary from RefSeq, UniProt

Involved in Golgi organization. Located in Golgi apparatus and plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.83

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.83LOEUF

pLI 0.002

Z-score 0.01

OE 0.99 (0.47–1.83)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.85Z-score

OE missense 1.29 (1.08–1.54)

89 obs / 69.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.99 (0.47–1.83)

0≤0.351.4

Missense OE?1.29 (1.08–1.54)

0≤0.61.4

Synonymous OE?1.15

0≤1.21.6

LoF obs/exp: 4 / 4.0Missense obs/exp: 89 / 69.1Syn Z: -0.66

Background carrier burden — how many people carry a rare variant somewhere in FAM174B?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 68

438 rare PASS variants

Rare truncating (LoF)

1 in 190

104 rare PASS variants

Rare synonymous (reference)

1 in 130

187 rare PASS variants

Rare missense and truncating variants are carried at similar rates in FAM174B; this gene does not show strong loss-of-function constraint by this measure. 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 110	1 in 460
South Asian	~43k	1 in 110	1 in 530
Remaining (unassigned)	~30k	1 in 53	1 in 450
European (Finnish)	~27k	1 in 230	1 in 3,000
Admixed American	~22k	1 in 70	1 in 1,400
African / African American	~21k	1 in 91	1 in 2,400
East Asian	~20k	1 in 100	1 in 410
Ashkenazi Jewish	~13k	1 in 540	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 88	1 in 560

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): 2 of 3 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 3.? see exons ↓