CLP1

Chr 11AR

cleavage factor polyribonucleotide kinase subunit 1

Also known as: HEAB, hClp1

NCBI Gene: 10978 ENSG00000172409 UniProt: Q92989 OMIM: 608757

The encoded protein is a multifunctional kinase that functions as a component of both the tRNA splicing endonuclease complex and the pre-mRNA cleavage complex II, playing essential roles in tRNA, mRNA, and siRNA maturation. Mutations cause pontocerebellar hypoplasia type 10 (PCH10), inherited in an autosomal recessive pattern. The pathogenic mechanism involves disrupted RNA processing affecting neuronal development and survival.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the Clp1 family. The encoded protein is a multifunctional kinase which is a component of the tRNA splicing endonuclease complex and a component of the pre-mRNA cleavage complex II. This protein is implicated in tRNA, mRNA, and siRNA maturation. Mutations in this gene are associated with pontocerebellar hypoplasia type 10 (PCH10). Alternatively splice transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2014]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Pontocerebellar hypoplasia, type 10MIM #615803

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Pontocerebellar hypoplasia, type 10; no ClinGen or GenCC tier

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.59

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.59LOEUF

pLI 0.203

Z-score 2.71

OE 0.26 (0.13–0.59)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.25Z-score

OE missense 0.60 (0.53–0.69)

152 obs / 252.8 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.26 (0.13–0.59)

0≤0.351.4

Missense OE?0.60 (0.53–0.69)

0≤0.61.4

Synonymous OE?0.82

0≤1.21.6

LoF obs/exp: 4 / 15.5Missense obs/exp: 152 / 252.8Syn Z: 1.36

Background carrier burden — how many people carry a rare variant somewhere in CLP1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 220

402 rare PASS variants

Rare truncating (LoF)

1 in 2,500

66 rare PASS variants

Rare synonymous (reference)

1 in 160

165 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CLP1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 280	1 in 2,800
South Asian	~43k	1 in 160	1 in 1,600
Remaining (unassigned)	~30k	1 in 150	1 in 1,800
European (Finnish)	~27k	1 in 290	≈ 1 in 27,000
Admixed American	~22k	1 in 240	1 in 2,500
African / African American	~21k	1 in 200	1 in 2,200
East Asian	~20k	1 in 160	1 in 3,300
Ashkenazi Jewish	~13k	1 in 690	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 290	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 2 coding exons well covered in gnomAD exomes and genomes.? see exons ↓