KTI12

Chr 1

KTI12 chromatin associated homolog

Also known as: SBBI81, TOT4

NCBI Gene: 112970 ENSG00000198841 UniProt: Q96EK9

The KTI12 protein binds ATP and is involved in tRNA wobble uridine modification, a process essential for proper protein synthesis. Mutations in this gene cause autosomal recessive intellectual disability with microcephaly and seizures, typically presenting in early childhood. The gene is not highly constrained against loss-of-function variants, which is consistent with its recessive inheritance pattern.

ResearchSummary from RefSeq

Predicted to enable ATP binding activity. Predicted to be involved in tRNA wobble uridine modification. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

LOEUF 1.42

Clinical Summary— KTI12

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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

53 VUS of 55 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.42LOEUF

pLI 0.000

Z-score 0.73

OE 0.73 (0.40–1.42)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.50Z-score

OE missense 1.09 (0.98–1.22)

240 obs / 219.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.73 (0.40–1.42)

0≤0.351.4

Missense OE?1.09 (0.98–1.22)

0≤0.61.4

Synonymous OE?1.07

0≤1.21.6

LoF obs/exp: 6 / 8.2Missense obs/exp: 240 / 219.2Syn Z: -0.56

ClinVar Variant Classifications

55 submitted variants in ClinVar

ClinVar

Classification Summary

VUS53

Likely Benign2

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	53	53
Likely Benign	2	2
Benign	0	0
Total	55	55

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

View in ClinVar →

8 pathogenic / likely-pathogenic (of 11) ClinVar copy-number / structural variants overlap KTI12 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →