ANKRD50

Chr 4

ankyrin repeat domain 50

The ANKRD50 protein facilitates endosome-to-plasma membrane trafficking and recycling of cargo proteins including the glucose transporter GLUT1. Mutations cause autosomal recessive intellectual disability with seizures and spasticity. This gene is highly constrained against loss-of-function variants, indicating it is essential for normal cellular function.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
2
Pubs (1 yr)
26
P/LP submissions
0%
P/LP missense
0.30
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical SummaryANKRD50
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
26 unique Pathogenic / Likely Pathogenic· 166 VUS of 208 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.30LOEUF
pLI 0.979
Z-score 5.49
OE 0.17 (0.100.30)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
0.70Z-score
OE missense 0.93 (0.870.99)
683 obs / 736.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.17 (0.100.30)
00.351.4
Missense OE0.93 (0.870.99)
00.61.4
Synonymous OE1.08
01.21.6
LoF obs/exp: 9 / 51.5Missense obs/exp: 683 / 736.8Syn Z: -1.06
DN
0.2997th %ile
GOF
0.3987th %ile
LOF
0.72top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.30

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

208 submitted variants in ClinVar

Classification Summary

Pathogenic23
Likely Pathogenic3
VUS166
Likely Benign7
23
Pathogenic
3
Likely Pathogenic
166
VUS
7
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
23
0
23
Likely Pathogenic
0
0
3
0
3
VUS
0
162
4
0
166
Likely Benign
0
2
1
4
7
Benign
0
0
0
0
0
Total0164314199

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

View in ClinVar →

Protein Context — Lollipop Plot

ANKRD50 · 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
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