SARM1
Chr 17sterile alpha and TIR motif containing 1
Also known as: HsTIR, MyD88-5, SAMD2, SARM, hSARM1
Enables NAD+ nucleosidase activity; NAD+ nucleosidase activity, cyclic ADP-ribose generating; and identical protein binding activity. Involved in NAD catabolic process and response to axon injury. Is active in mitochondrion. [provided by Alliance of Genome Resources, Apr 2025]
Clinical Summary— SARM1
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Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
13 Pathogenic / Likely Pathogenic· 103 VUS of 187 total submissions
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.14LOEUF
pLI 0.000
Z-score 1.03
OE 0.77 (0.53–1.14)
Highly tolerant — LoF variants common in population
Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.90Z-score
OE missense 0.72 (0.65–0.80)
269 obs / 372.3 exp
Mild missense constraint
Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.77 (0.53–1.14)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.72 (0.65–0.80)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.83
0≤1.21.6
LoF obs/exp: 18 / 23.4Missense obs/exp: 269 / 372.3Syn Z: 1.69
ClinVar Variant Classifications
187 submitted variants in ClinVar
Classification Summary
Pathogenic9
Likely Pathogenic4
VUS103
Likely Benign41
Benign27
Conflicting3
9
Pathogenic
4
Likely Pathogenic
103
VUS
41
Likely Benign
27
Benign
3
Conflicting
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 3 | 1 | 5 | 0 | 9 |
Likely Pathogenic | 2 | 1 | 1 | 0 | 4 |
VUS | 1 | 32 | 69 | 1 | 103 |
Likely Benign | 0 | 2 | 20 | 19 | 41 |
Benign | 0 | 0 | 27 | 0 | 27 |
Conflicting | — | 3 | |||
| Total | 6 | 36 | 122 | 20 | 187 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SARM1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
OMIM — Genotype-Phenotype Relationships
1 OMIM entry
STERILE ALPHA AND TIR MOTIFS-CONTAINING PROTEIN 1; SARM1
MIM #607732 · *
External Resources
Links to major genomics databases and tools
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
Peripheral neuropathy: from guidelines to clinical practise.
Jordan B et al.·Curr Opin Oncol
2025Review
METTL1-mediated m(7)G methylation of Sarm1 mRNA promotes macrophage inflammatory responses and multiple organ injury.
Hou C et al.·Sci Immunol
2025
SARM1 activation promotes axonal degeneration via a two-step phase transition.
Zhang W et al.·Nat Chem Biol
2026
SARM1 loss protects retinal ganglion cells in a mouse model of autosomal dominant optic atrophy.
Ding C et al.·J Clin Invest
2025Functional
Axonal degeneration in chemotherapy-induced peripheral neurotoxicity: clinical and experimental evidence.
Park SB et al.·J Neurol Neurosurg Psychiatry
2023Review
A CRISPR activation screen reveals a cilia disassembly pathway mutated in focal cortical dysplasia.
Elliott SD et al.·Sci Adv
2025
TLR4 and SARM1 modulate survival and chemoresistance in an HPV-positive cervical cancer cell line.
Morale MG et al.·Sci Rep
2022
Constitutively active SARM1 variants that induce neuropathy are enriched in ALS patients.
Bloom AJ et al.·Mol Neurodegener
2022Cohort
Therapeutic opportunities and pitfalls in the treatment of axon degeneration.
Simon DJ et al.·Curr Opin Neurol
2018Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Sarm1-containing extrachromosomal circular DNA promotes aging-associated cardiac fibrosis via TGF-β/Smad activation.
Zhang Y et al.·J Mol Cell Biol
2026
Increased synaptic turnover in injured cortical axons: exploring the role of SARM1 ablation.
Izadi E et al.·Front Synaptic Neurosci
2026
Targeting the SARM1-NAD⁺ axis: A review of new strategy for reversing the imbalance of energy and mitochondrial homeostasis in metabolic diseases.
Xiong A et al.·Pharmacol Res
2026Review
Caspase-3 cleaves and activates the NADase SARM1 to promote apoptosis, linking two cell death mechanisms.
Shi J et al.·Proc Natl Acad Sci U S A
2026Open AccessFunctional
Hypoxia-inducible factor 1 protects neurons from Sarm1-mediated neurodegeneration.
Meraner P et al.·Cell Rep
2026
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
Distinct developmental and degenerative functions of SARM1 require NAD+ hydrolase activity
Brace EJ et al.·PLoS Genet
2022
Multifaceted roles of SARM1 in axon degeneration and signaling
Waller TJ et al.·Front Cell Neurosci
2022
Synergistic Protection of Retinal Ganglion Cells (RGCs) by SARM1 Inactivation with CNTF in a Rodent Model of Nonarteritic Anterior Ischemic Optic Neuropathy
Guo Y et al.·Cells
2024Functional
SARM1 detection in myelinating glia: sarm1/Sarm1 is dispensable for PNS and CNS myelination in zebrafish and mice
Fazal SV et al.·Front Cell Neurosci
2023Functional
Serum SARM1 Levels and Diabetic Peripheral Neuropathy in Type 2 Diabetes: Correlation with Clinical Neuropathy Scales and Nerve Conduction Studies and Impact of COVID-19 vaccination
Alrawaili MS et al.·Vaccines (Basel)
2024
Genetic ablation of Sarm1 attenuates expression and mislocalization of phosphorylated TDP-43 after mouse repetitive traumatic brain injury
Dogan EO et al.·Acta Neuropathol Commun
2023Functional
Base-Exchange Enabling the Visualization of SARM1 Activities in Sciatic Nerve-Injured Mice
Huang K et al.·ACS Sens
2023
A Novel NAD Signaling Mechanism in Axon Degeneration and its Relationship to Innate Immunity
Hopkins EL et al.·Front Mol Biosci
2021Functional
Genetic inactivation of SARM1 axon degeneration pathway improves outcome trajectory after experimental traumatic brain injury based on pathological, radiological, and functional measures
Bradshaw DV Jr et al.·Acta Neuropathol Commun
2021Functional
Top 10 full-text resultsSearch PubTator3 ↗
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools