KPTN

Chr 19AR

kaptin, actin binding protein

Also known as: 2E4, KICS4, MRT41

NCBI Gene: 11133 ENSG00000118162 UniProt: Q9Y664 OMIM: 615620

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a filamentous-actin-associated protein, which is involved in actin dynamics and plays an important role in neuromorphogenesis. This protein is part of the KICSTOR protein complex that localizes to lysosomes. Mutations in this gene result in an autosomal recessive form of intellectual disability. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2017]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.811 OMIM phenotype

Clinical Summary— KPTN

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Gene-Disease Validity (ClinGen)

complex neurodevelopmental disorder · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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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

23 unique Pathogenic / Likely Pathogenic· 114 VUS of 233 total submissions

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GeneReview available — KPTN

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.81LOEUF

pLI 0.000

Z-score 2.28

OE 0.50 (0.32–0.81)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.45Z-score

OE missense 0.75 (0.67–0.84)

200 obs / 266.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.50 (0.32–0.81)

0≤0.351.4

Missense OE?0.75 (0.67–0.84)

0≤0.61.4

Synonymous OE?0.90

0≤1.21.6

LoF obs/exp: 12 / 24.0Missense obs/exp: 200 / 266.4Syn Z: 0.83

ClinVar Variant Classifications

233 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic13

Likely Pathogenic10

VUS114

Likely Benign60

Benign17

Conflicting9

Pathogenic

Likely Pathogenic

114

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	12	0	1	0	13
Likely Pathogenic	8	2	0	0	10
VUS	5	99	9	1	114
Likely Benign	0	4	22	34	60
Benign	0	1	10	6	17
Conflicting	—				9
Total	25	106	42	41	223

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

View in ClinVar →

13 pathogenic / likely-pathogenic (of 19) ClinVar copy-number / structural variants overlap KPTN — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →