HEATR4

protein-coding

HEAT repeat containing 4, the group of Armadillo like helical domain containing

Gene summary

Predicted to enable oxidoreductase activity. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_001220484.1

Inheritance

—

ClinVar variants

U:169B:19

Top phenotype

Generalized hypotonia

gnomAD constraint

pLI —, LoF o/e 0.94

Max pathogenic AF

—

Genomic locus

chr14:73,478,484-73,558,947

External References & Databases

Ensembl (ENSG00000187105)

Transcript & Mutation Effects

hg38 • Region Span ~80.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to HEATR4 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 240

not providedTotal: 16

Generalized hypotoniaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001220484.1. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				2 clinvar		2
missense			167 clinvar	17 clinvar		184
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	169	19	0	188

Highest pathogenic variant AF is 9.174413e-7

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 12 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001220484.1	RefSeq	NP_001207413.1	16	MANE Select
ENST00000553558.6	Ensembl	ENSP00000450444.2	16	MANE Select
NM_203309.2	RefSeq	NP_976054.2	16	Standard
ENST00000334988.2	Ensembl	ENSP00000335447.2	16	Standard

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000553558
Coding exons: 16
Length: 80463
Individuals with no LoFs: 124776
Homozygous LoFs: 10
Heterozygous LoFs: 962
Defined: 125748
p: 0.00387

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.329	554	576	0.961	0.0000322	6679
Missense (PolyPhen)		138	150.52	0.91679		1887
Synonymous	0.786	197	212	0.931	0.0000109	2027
Loss of Function	0.388	46	48.9	0.940	0.00000251	550

Population LoF Frequency

Population	CAF	p-value	Status
African	0.035	0.035	notable
Latino/Admixed American	0.0027	0.0027	notable
Ashkenazi Jewish	0.0092	0.0092	notable
East Asian	0.0022	0.0022	notable
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.0012	0.0012	notable
South Asian	0.0015	0.0011	notable
Other	0.0026	0.0026	notable

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.0751

Intolerance Scores

LoFtool: 0.988
RVIS EVS: -0.01
RVIS percentile EVS: 52.38

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.0864

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium