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KIAA0754

Chr 1

KIAA0754

NCBI Gene: 643314 UniProt: Q9UPN3

This gene encodes an F-actin-binding protein that cross-links actin to other cytoskeletal proteins, binds microtubules, regulates focal adhesion dynamics, and plays essential roles in neurite outgrowth and spine formation during brain development. Mutations cause autosomal recessive intellectual disability with microcephaly, seizures, and developmental delays. The protein's critical functions in cytoskeletal organization and neuronal development explain the severe neurodevelopmental phenotype observed in affected individuals.

ResearchSummary from UniProt

ResearchGenerating clinical summary…

LOEUF 0.61

Clinical Summary— KIAA0754

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.

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ClinVar Variants

10 VUS of 21 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.61LOEUF

pLI 0.085

Z-score 2.74

OE 0.29 (0.15–0.61)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.58Z-score

OE missense 0.93 (0.87–1.00)

586 obs / 627.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.29 (0.15–0.61)

0≤0.351.4

Missense OE?0.93 (0.87–1.00)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 5 / 17.3Missense obs/exp: 586 / 627.1Syn Z: 0.41

ClinVar Variant Classifications

21 submitted variants in ClinVar

ClinVar

Classification Summary

VUS10

Likely Benign8

Benign3

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	10	0	10
Likely Benign	6	2	8
Benign	3	0	3
Total	19	2	21

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

View in ClinVar →

8 pathogenic / likely-pathogenic (of 14) ClinVar copy-number / structural variants overlap KIAA0754 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →