HEATR1

Chr 1

HEAT repeat containing 1

Also known as: BAP28, UTP10

NCBI Gene: 55127 ENSG00000119285 UniProt: Q9H583 OMIM: 620390

HEATR1 encodes a ribosome biogenesis factor that is required for processing of pre-18S ribosomal RNA and assembly of the small ribosomal subunit in the nucleolus. Mutations cause autosomal recessive neurodevelopmental disorders with intellectual disability and seizures, typically presenting in early childhood. This gene is highly constrained against loss-of-function variants, reflecting its essential role in ribosome biogenesis.

OMIM ResearchSummary from RefSeq, UniProt

Enables RNA binding activity. Involved in several processes, including positive regulation of RNA metabolic process; protein localization to nucleolus; and ribosomal small subunit biogenesis. Located in fibrillar center and mitochondrion. Part of small-subunit processome. Implicated in pancreatic ductal carcinoma. Biomarker of glioblastoma. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.14

Clinical Summary— HEATR1

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

280 VUS of 408 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.14LOEUF

pLI 1.000

Z-score 8.81

OE 0.08 (0.04–0.14)

Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?

0.09Z-score

OE missense 0.99 (0.94–1.04)

1073 obs / 1081.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.08 (0.04–0.14)

0≤0.351.4

Missense OE?0.99 (0.94–1.04)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 8 / 105.7Missense obs/exp: 1073 / 1081.1Syn Z: -0.33

This gene — mechanism propensity

0.3594th %ile

GOF

0.3094th %ile

LOF

0.65top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.14

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

408 submitted variants in ClinVar

ClinVar

Classification Summary

VUS280

Likely Benign27

Benign11

280

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	280	0	0	280
Likely Benign	20	1	6	27
Benign	5	3	3	11
Total	305	4	9	318

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

View in ClinVar →

48 pathogenic / likely-pathogenic (of 67) ClinVar copy-number / structural variants overlap HEATR1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →