KATNIP

Chr 16AR

katanin interacting protein

Also known as: JBTS26, KIAA0556

NCBI Gene: 23247 ENSG00000047578 OMIM: 616650

This gene encodes a ciliary protein that localizes to the ciliary axoneme and tip, and may influence microtubule stability through interaction with the katanin complex. Mutations cause Joubert syndrome 26, an autosomal recessive ciliopathy characterized by distinctive mid-hindbrain and cerebellar malformations often accompanied by broader ciliopathy symptoms. Patient-derived fibroblasts show reduced ciliogenesis with abnormally long cilia, consistent with the protein's role in ciliary function.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a novel, evolutionarily conserved, ciliary protein. In human hTERT-RPE1 cells, the protein is found at the base of cilia, decorating the ciliary axoneme, and enriched at the ciliary tip. The protein binds to microtubules in vitro and regulates their stability when it is overexpressed. A null mutation in this gene has been associated with Joubert syndrome, a recessive disorder that is characterized by a distinctive mid-hindbrain and cerebellar malformation and is also often associated with wider ciliopathy symptoms. Consistently, in a serum-starvation ciliogenesis assay, human fibroblast cells derived from patients with the mutation display a reduced number of ciliated cells with abnormally long cilia. [provided by RefSeq, Feb 2016]

GeneReviews OMIM ResearchGenerating clinical summary…

ARLOEUF 0.911 OMIM phenotype

Clinical Summary— KATNIP

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Gene-Disease Validity (ClinGen)

ciliopathy · 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

48 unique Pathogenic / Likely Pathogenic· 403 VUS of 832 total submissions

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GeneReview available — KATNIP

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?

0.91LOEUF

pLI 0.000

Z-score 2.23

OE 0.73 (0.59–0.91)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.11Z-score

OE missense 1.01 (0.96–1.06)

987 obs / 977.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.73 (0.59–0.91)

0≤0.351.4

Missense OE?1.01 (0.96–1.06)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 57 / 78.3Missense obs/exp: 987 / 977.2Syn Z: -0.18

ClinVar Variant Classifications

832 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20

Likely Pathogenic28

VUS403

Likely Benign285

Benign57

Conflicting10

Pathogenic

Likely Pathogenic

403

VUS

285

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	16	0	4	0	20
Likely Pathogenic	26	2	0	0	28
VUS	2	390	6	5	403
Likely Benign	1	43	66	175	285
Benign	0	15	24	18	57
Conflicting	—				10
Total	45	450	100	198	803

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

View in ClinVar →

33 pathogenic / likely-pathogenic (of 47) ClinVar copy-number / structural variants overlap KATNIP — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →