FAM200B

Chr 4

family with sequence similarity 200 member B

Also known as: C4orf53

The FAM200B protein function is not well characterized, but mutations cause autosomal recessive neurodevelopmental disorder with seizures, spastic quadriplegia, and brain malformations including delayed myelination and corpus callosum abnormalities. The gene shows moderate constraint against loss-of-function variants, and affected individuals typically present in infancy with severe developmental delays and neurological impairment.

0
Active trials
2
Pubs (1 yr)
52
P/LP submissions
P/LP missense
1.29
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryFAM200B
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
52 unique Pathogenic / Likely Pathogenic· 9 VUS of 72 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.29LOEUF
pLI 0.000
Z-score 0.63
OE 0.84 (0.561.29)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.89Z-score
OE missense 0.86 (0.770.95)
260 obs / 303.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.84 (0.561.29)
00.351.4
Missense OE0.86 (0.770.95)
00.61.4
Synonymous OE0.80
01.21.6
LoF obs/exp: 15 / 17.9Missense obs/exp: 260 / 303.6Syn Z: 1.63
DN
0.6842th %ile
GOF
0.6443th %ile
LOF
0.2775th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

72 submitted variants in ClinVar

Classification Summary

Pathogenic49
Likely Pathogenic3
VUS9
Benign1
49
Pathogenic
3
Likely Pathogenic
9
VUS
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
49
Likely Pathogenic
3
VUS
9
Likely Benign
0
Benign
1
Total62

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

FAM200B · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found