FAM178B

Chr 2

family with sequence similarity 178 member B

NCBI Gene: 51252 ENSG00000168754 UniProt: Q8IXR5

The protein function of FAM178B is not well-characterized in the provided data. Mutations in FAM178B cause autosomal recessive developmental delay and intellectual disability. The gene shows low constraint against loss-of-function variants based on population genetics data.

Research

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.93

LOEUF

GOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.93LOEUF

pLI 0.000

Z-score 1.93

OE 0.66 (0.48–0.93)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.01Z-score

OE missense 0.85 (0.77–0.94)

300 obs / 353.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.66 (0.48–0.93)

0≤0.351.4

Missense OE?0.85 (0.77–0.94)

0≤0.61.4

Synonymous OE?0.80

0≤1.21.6

LoF obs/exp: 25 / 37.8Missense obs/exp: 300 / 353.2Syn Z: 1.97

Background carrier burden — how many people carry a rare variant somewhere in FAM178B?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 66

833 rare PASS variants

Rare truncating (LoF)

1 in 560

175 rare PASS variants

Rare synonymous (reference)

1 in 95

389 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for FAM178B. 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 79	1 in 580
South Asian	~43k	1 in 52	1 in 430
Remaining (unassigned)	~30k	1 in 49	1 in 730
European (Finnish)	~27k	1 in 160	1 in 670
Admixed American	~22k	1 in 55	1 in 410
African / African American	~21k	1 in 48	1 in 460
East Asian	~20k	1 in 54	1 in 350
Ashkenazi Jewish	~13k	1 in 85	1 in 700
Middle Eastern	~2,884	1 in 58	1 in 320

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 16 of 17 coding exons well covered in gnomAD exomes; exon 8 marginal. Genomes: all 17.? see exons ↓