The KIAA1958 protein function remains poorly characterized, but mutations cause autosomal recessive spastic paraplegia with intellectual disability and seizures. This gene shows moderate constraint against loss-of-function variants, and affected individuals typically present in early childhood with progressive spasticity primarily affecting the lower extremities along with developmental delays.

LOEUF 0.64
Clinical SummaryKIAA1958
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.34) despite low pLI — interpret in context.
📋
ClinVar Variants
31 unique Pathogenic / Likely Pathogenic· 49 VUS of 90 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.64LOEUF
pLI 0.011
Z-score 2.75
OE 0.34 (0.190.64)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.24Z-score
OE missense 0.83 (0.760.91)
342 obs / 413.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.34 (0.190.64)
00.351.4
Missense OE0.83 (0.760.91)
00.61.4
Synonymous OE1.02
01.21.6
LoF obs/exp: 7 / 20.4Missense obs/exp: 342 / 413.1Syn Z: -0.15

ClinVar Variant Classifications

90 submitted variants in ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic4
VUS49
Likely Benign5
Benign1
27
Pathogenic
4
Likely Pathogenic
49
VUS
5
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
27
0
27
Likely Pathogenic
0
0
4
0
4
VUS
0
44
5
0
49
Likely Benign
0
2
1
2
5
Benign
0
0
1
0
1
Total04638286

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

View in ClinVar →

Protein Context — Lollipop Plot

KIAA1958 · 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