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…

LOFmechanismARLOEUF 1.141 OMIM phenotype

Clinical Summary— FAM177A1

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

8 unique Pathogenic / Likely Pathogenic· 40 VUS of 67 total submissions

Explore recent and relevant literature in Research Assistant →

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

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

moderateFAM177A1-related neurodevelopmental disorder with macrocephalyLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6454th %ile

GOF

0.74top 25%

LOF

0.2872th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

67 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6

Likely Pathogenic2

VUS40

Likely Benign6

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	3	0	3	0	6
Likely Pathogenic	1	0	1	0	2
VUS	1	39	0	0	40
Likely Benign	0	2	1	3	6
Benign	0	0	0	0	0
Total	5	41	5	3	54

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

25 pathogenic / likely-pathogenic (of 35) ClinVar copy-number / structural variants overlap FAM177A1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →