HENMT1

protein-coding

HEN methyltransferase 1, the group of 7BS 2'O-ribose DNA/RNA methyltransferases

Gene summary

Enables small RNA 2'-O-ribose methyltransferase activity. Involved in RNA methylation. Predicted to be located in P granule. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

C1orf59

MANE transcript

NM_001102592.2

Inheritance

—

ClinVar variants

P:2U:57B:10

Top phenotype

Azoospermia

gnomAD constraint

pLI —, LoF o/e 1.01

Max pathogenic AF

—

Genomic locus

chr1:108,648,290-108,661,526

External References & Databases

Ensembl (ENSG00000162639)

Transcript & Mutation Effects

hg38 • Region Span ~13.2 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 HENMT1 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 62

not providedTotal: 4

AzoospermiaTotal: 2

Male infertilityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001102592.2. 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	1 clinvar	3
missense	1 clinvar		56 clinvar	5 clinvar	2 clinvar	64
nonsense	1 clinvar		1 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	2	0	57	7	3	69

Highest pathogenic variant AF is 0.00000806828

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 31 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001102592.2	RefSeq	NP_001096062.1	7	MANE Select
ENST00000651461.1	Ensembl	ENSP00000499017.1	7	MANE Select
NM_144584.3	RefSeq	NP_653185.2	7	Standard
ENST00000370031.5	Ensembl	ENSP00000359048.1	8	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
henmt1	Danio rerio	Structure: RNA 3' uridylation Quality: increased occurrence abnormal

Gene / Model

Organism

Observed Phenotype

henmt1

Danio rerio

Structure: RNA 3' uridylation

Quality: increased occurrence

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Gene expression (Transcription)
PIWI-interacting RNA (piRNA) biogenesis
Gene Silencing by RNA

Biological Process

RNA methylation
production of siRNA involved in RNA interference
piRNA metabolic process

Molecular Function

RNA binding
protein binding
O-methyltransferase activity
RNA methyltransferase activity
metal ion binding

Cellular Component

nucleus
cytoplasm
P granule

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000370032
Coding exons: 7
Length: 13237
Individuals with no LoFs: 125706
Homozygous LoFs: 0
Heterozygous LoFs: 42
Defined: 125748
p: 0.000167

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0585	213	215	0.989	0.0000114	2554
Missense (PolyPhen)		40	46.078	0.8681		560
Synonymous	0.113	79	80.3	0.984	0.00000410	765
Loss of Function	-0.0435	14	13.8	1.01	6.71e-7	178

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00026	0.00026	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00050	0.00049	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00014	0.00014	rare
South Asian	0.00020	0.00020	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Methyltransferase that adds a 2'-O-methyl group at the 3'-end of piRNAs, a class of 24 to 30 nucleotide RNAs that are generated by a Dicer-independent mechanism and are primarily derived from transposons and other repeated sequence elements. This probably protects the 3'-end of piRNAs from uridylation activity and subsequent degradation. Stabilization of piRNAs is essential for gametogenesis. {ECO:0000250|UniProtKB:Q8CAE2}.;

Recessive Scores

pRec: 0.0972

Intolerance Scores

RVIS EVS: 0.8
RVIS percentile EVS: 87.49

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