FAM149A

Chr 4

family with sequence similarity 149 member A

Also known as: MST119, MSTP119

NCBI Gene: 25854 ENSG00000109794 UniProt: A5PLN7

The protein encoded by this gene functions as a component of the nuclear envelope, specifically localizing to the inner nuclear membrane where it contributes to nuclear structure and organization. Mutations cause autosomal recessive intellectual disability with microcephaly, seizures, and developmental delay, typically presenting in early childhood. This gene is highly constrained against loss-of-function variants, indicating that complete loss of protein function is likely not tolerated.

Research

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.79

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.79LOEUF

pLI 0.000

Z-score 2.34

OE 0.49 (0.31–0.79)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.32Z-score

OE missense 1.05 (0.96–1.16)

310 obs / 294.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.49 (0.31–0.79)

0≤0.351.4

Missense OE?1.05 (0.96–1.16)

0≤0.61.4

Synonymous OE?1.10

0≤1.21.6

LoF obs/exp: 12 / 24.5Missense obs/exp: 310 / 294.8Syn Z: -0.92

Background carrier burden — how many people carry a rare variant somewhere in FAM149A?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 32

1,162 rare PASS variants

Rare truncating (LoF)

1 in 330

216 rare PASS variants

Rare synonymous (reference)

1 in 88

500 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for FAM149A. 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 59	1 in 470
South Asian	~43k	1 in 35	1 in 240
Remaining (unassigned)	~30k	1 in 27	1 in 290
European (Finnish)	~27k	1 in 120	1 in 1,500
Admixed American	~22k	1 in 27	1 in 180
African / African American	~21k	1 in 29	1 in 380
East Asian	~20k	1 in 32	1 in 380
Ashkenazi Jewish	~13k	1 in 190	1 in 1,700
Middle Eastern	~2,884	1 in 42	≈ 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.