KPTN

Chr 19AR

kaptin, actin binding protein

Also known as: 2E4, KICS4, MRT41

This gene encodes a filamentous-actin-associated protein that functions as part of the KICSTOR complex to regulate mTORC1 signaling at lysosomes in response to amino acid availability. Mutations cause autosomal recessive intellectual developmental disorder (intellectual developmental disorder, autosomal recessive 41). The gene shows low constraint against loss-of-function variants (pLI near 0), consistent with its recessive inheritance pattern.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.811 OMIM phenotype
Clinical SummaryKPTN
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Gene-Disease Validity (ClinGen)
complex neurodevelopmental disorder · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
36 unique Pathogenic / Likely Pathogenic· 118 VUS of 252 total submissions
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GeneReview available — KPTN
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.81LOEUF
pLI 0.000
Z-score 2.28
OE 0.50 (0.320.81)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.45Z-score
OE missense 0.75 (0.670.84)
200 obs / 266.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.50 (0.320.81)
00.351.4
Missense OE0.75 (0.670.84)
00.61.4
Synonymous OE0.90
01.21.6
LoF obs/exp: 12 / 24.0Missense obs/exp: 200 / 266.4Syn Z: 0.83

ClinVar Variant Classifications

252 submitted variants in ClinVar

Classification Summary

Pathogenic23
Likely Pathogenic13
VUS118
Likely Benign61
Benign17
Conflicting9
23
Pathogenic
13
Likely Pathogenic
118
VUS
61
Likely Benign
17
Benign
9
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
12
0
11
0
23
Likely Pathogenic
8
2
3
0
13
VUS
5
99
13
1
118
Likely Benign
0
4
23
34
61
Benign
0
1
10
6
17
Conflicting
9
Total251066041241

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

View in ClinVar →

Protein Context — Lollipop Plot

KPTN · 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 →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC