FAM177A1

Chr 14AR

family with sequence similarity 177 member A1

Also known as: C14orf24, NEDWMG

NCBI Gene: 283635 ENSG00000151327 UniProt: Q8N128 OMIM: 619181

This gene encodes a member of a conserved protein family with unknown specific function. Biallelic mutations cause autosomal recessive neurodevelopmental disorder with white matter abnormalities and gait disturbance. The gene shows tolerance to loss-of-function variation in the general population (pLI 0.001, LOEUF 1.139).

OMIM ResearchSummary from RefSeq, OMIM

This gene encodes a member of a conserved protein family. Alternative splicing results in multiple transcript variants. This gene is thought to be associated with susceptibility to juvenile idiopathic arthritis. [provided by RefSeq, Apr 2017]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with white matter abnormalities and gait disturbanceMIM #621152

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Neurodevelopmental disorder with white matter abnormalities and gait disturbance; no ClinGen or GenCC tier

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.14

LOEUF

LOF

Mechanism· G2P

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.14LOEUF

pLI 0.001

Z-score 1.26

OE 0.58 (0.32–1.14)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.30Z-score

OE missense 1.08 (0.93–1.25)

131 obs / 121.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.58 (0.32–1.14)

0≤0.351.4

Missense OE?1.08 (0.93–1.25)

0≤0.61.4

Synonymous OE?1.16

0≤1.21.6

LoF obs/exp: 6 / 10.4Missense obs/exp: 131 / 121.6Syn Z: -0.80

Background carrier burden — how many people carry a rare variant somewhere in FAM177A1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 150

334 rare PASS variants

Rare truncating (LoF)

1 in 800

70 rare PASS variants

Rare synonymous (reference)

1 in 250

114 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for FAM177A1. 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 280	1 in 2,500
South Asian	~43k	1 in 150	1 in 950
Remaining (unassigned)	~30k	1 in 110	1 in 1,500
European (Finnish)	~27k	1 in 680	none seen
Admixed American	~22k	1 in 150	1 in 1,100
African / African American	~21k	1 in 140	1 in 510
East Asian	~20k	1 in 130	1 in 610
Ashkenazi Jewish	~13k	1 in 690	1 in 1,000
Middle Eastern	~2,884	1 in 190	1 in 550

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 5 coding exons well covered in gnomAD exomes and genomes.? see exons ↓