KIAA1549

Chr 7AR

KIAA1549

Also known as: RP86

NCBI Gene: 57670 ENSG00000122778 UniProt: Q9HCM3

The protein encoded by this gene belongs to the UPF0606 family. This gene has been found to be fused to the BRAF oncogene in many cases of pilocytic astrocytoma. The fusion results from 2Mb tandem duplications at 7q34. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2012]

Primary Disease Associations & Inheritance

Retinitis pigmentosa 86MIM #618613

577

ClinVar variants

Pathogenic / LP

0.99

pLI score· haploinsufficient

Active trials

Clinical Summary— KIAA1549

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Gene-Disease Validity (ClinGen)

retinitis pigmentosa 86 · ARStrong

Strong evidence — appropriate for clinical testing

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

9 Pathogenic / Likely Pathogenic· 345 VUS of 577 total submissions

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Clinical Trials

8 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.

0.29LOEUF

pLI 0.986

Z-score 6.15

OE 0.18 (0.12–0.29)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.

-0.09Z-score

OE missense 1.01 (0.96–1.06)

1121 obs / 1112.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.

LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.18 (0.12–0.29)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.01 (0.96–1.06)

0≤0.61.4

Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.07

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	0	5	0	6
Likely Pathogenic	2	0	1	0	3
VUS	5	321	10	9	345
Likely Benign	0	10	42	162	214
Benign	0	0	0	0	0
Conflicting	—				9
Total	8	331	58	171	577

KIAA1549

Primary Disease Associations & Inheritance

Population Genetics & Constraint

ClinVar Variant Classifications

Classification Summary

Curated Variants Distribution

Protein Context — Lollipop Plot

DECIPHER · Gene2Phenotype

Gene2Phenotype Curations

OMIM — Genotype-Phenotype Relationships

Gene Overview

ClinGen Curation

Disease Associations

External Resources

Variant Interpretation

Population Databases

Gene Resources

Expert Curation

Clinical Trials

External Resources

Variant Interpretation

Population Databases

Gene Resources

Expert Curation