R3HDM4

protein-coding

R3H domain containing 4

Gene summary

Predicted to enable nucleic acid binding activity. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

C19orf22

MANE transcript

NM_138774.4

Inheritance

—

ClinVar variants

U:57B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.57

Max pathogenic AF

—

Genomic locus

chr19:896,503-913,245

External References & Databases

Ensembl (ENSG00000198858)

Transcript & Mutation Effects

hg38 • Region Span ~16.7 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 R3HDM4 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 55

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_138774.4. 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			1 clinvar			1
missense			56 clinvar	1 clinvar		57
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	57	1	0	58

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 33 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_138774.4	RefSeq	NP_620129.2	8	MANE Select
ENST00000361574.10	Ensembl	ENSP00000355385.4	8	MANE Select
ENST00000587975.2	Ensembl	ENSP00000464744.1	8	Standard
ENST00000587975.3	Ensembl	ENSP00000464744.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Molecular Function

nucleic acid binding

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000361574
Coding exons: 8
Length: 16738
Individuals with no LoFs: 125565
Homozygous LoFs: 1
Heterozygous LoFs: 31
Defined: 125597
p: 0.000127

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.532	177	158	1.12	0.0000112	1679
Missense (PolyPhen)		66	68.924	0.95757		632
Synonymous	-1.36	82	67.8	1.21	0.00000442	566
Loss of Function	1.38	7	12.2	0.573	5.97e-7	155

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000093	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.00024	0.00023	rare
European (Non-Finnish)	0.00018	0.00016	rare
South Asian	0.00010	0.000098	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.109

Intolerance Scores

RVIS EVS: 0.26
RVIS percentile EVS: 70.44

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

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