SARM1

protein-coding

sterile alpha and TIR motif containing 1, the group of Armadillo like helical domain containing|TIR domain containing|Sterile alpha motif domain containing

Gene summary

Enables double-stranded DNA binding activity; hydrolase activity, hydrolyzing N-glycosyl compounds; and identical protein binding activity. Involved in NAD+ catabolic process; positive regulation of programmed cell death; and response to axon injury. Located in cytoplasm. Is active in mitochondrion. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_015077.4

Inheritance

—

ClinVar variants

U:12B:2

Top phenotype

Congenital defect of folate absorption

gnomAD constraint

pLI —, LoF o/e 0.77

Max pathogenic AF

—

Genomic locus

chr17:28,364,356-28,404,049

External References & Databases

Ensembl (ENSG00000004139)

Transcript & Mutation Effects

hg38 • Region Span ~39.7 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 SARM1 variants in ClinVar

5 Conditions Cataloged

Congenital defect of folate absorptionTotal: 24

not providedTotal: 3

not specifiedTotal: 2

SARM1-related disorderTotal: 1

Amyotrophic lateral sclerosisTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015077.4. 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	2 clinvar		3
missense			9 clinvar			9
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	12	2	0	14

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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_015077.4	RefSeq	NP_055892.2	9	MANE Select
ENST00000585482.6	Ensembl	ENSP00000468032.2	9	MANE Select
ENST00000578128.5	Ensembl	ENSP00000462479.1	5	Standard
ENST00000579593.1	Ensembl	ENSP00000462228.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Regulation of toll-like receptor signaling pathway
Toll Like Receptor 3 (TLR3) Cascade
Toll-Like Receptors Cascades
Innate Immune System
Immune System

Biological Process

signal transduction
response to glucose
positive regulation of signal transduction
negative regulation of MyD88-independent toll-like receptor signaling pathway
regulation of apoptotic process

Molecular Function

protein binding
signaling adaptor activity

Cellular Component

cytoplasm
mitochondrion
cytosol
microtubule
cell junction

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000457710
Coding exons: 9
Length: 36688
Individuals with no LoFs: 5545
Homozygous LoFs: 120044
Heterozygous LoFs: 4
Defined: 125593
p: 0.790

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.90	269	372	0.722	0.0000226	4301
Missense (PolyPhen)		107	152.61	0.70113		1712
Synonymous	1.69	141	169	0.834	0.0000105	1511
Loss of Function	1.03	18	23.4	0.770	0.00000104	278

Population LoF Frequency

Population	CAF	p-value	Status
African	2.0	0.68	notable
Latino/Admixed American	2.0	0.83	notable
Ashkenazi Jewish	2.0	0.79	notable
East Asian	2.0	0.83	notable
Finnish	2.0	0.82	notable
European (Non-Finnish)	2.0	0.79	notable
South Asian	2.0	0.77	notable
Other	2.0	0.81	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Negative regulator of MYD88- and TRIF-dependent toll- like receptor signaling pathway which plays a pivotal role in activating axonal degeneration following injury. Promotes Wallerian degeneration an injury-induced axonal death pathway which involves degeneration of an axon distal to the injury site. Can activate neuronal death in response to stress. Regulates dendritic arborization through the MAPK4-JNK pathway. Involved in innate immune response. Inhibits both TICAM1/TRIF- and MYD88- dependent activation of JUN/AP-1, TRIF-dependent activation of NF- kappa-B and IRF3, and the phosphorylation of MAPK14/p38. {ECO:0000269|PubMed:15123841, ECO:0000269|PubMed:16964262, ECO:0000269|PubMed:16985498, ECO:0000269|PubMed:20306472}.;

Recessive Scores

pRec: 0.125

Essentials

Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.779

Gene Damage Prediction

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