SARM1

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

Basic information

Region (hg38): 17:28364355-28404049

Links

ENSG00000004139 ∙ NCBI:23098 ∙ OMIM:607732 ∙ HGNC:17074 ∙ Uniprot:Q6SZW1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SARM1 gene.

• Congenital defect of folate absorption (109 variants)
• not provided (50 variants)
• not specified (5 variants)
• Inborn genetic diseases (5 variants)
• Amyotrophic lateral sclerosis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SARM1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1			1
missense			7			7
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding	2	2	100	21	27	152
Total	2	2	108	21	27

Highest pathogenic variant AF is 0.0000854

Variants in SARM1

This is a list of pathogenic ClinVar variants found in the SARM1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-28364359-G-C		not specified	Uncertain significance (Jul 14, 2023)
17-28364393-A-G		not specified	Likely benign (Oct 14, 2023)
17-28364549-C-T		not specified	Uncertain significance (Jan 06, 2023)
17-28364801-C-G		not specified	Uncertain significance (Jun 05, 2023)
17-28364834-G-C		not specified	Uncertain significance (Apr 18, 2023)
17-28364929-G-A		not specified	Uncertain significance (Nov 14, 2023)
17-28364953-C-T		not specified	Uncertain significance (Dec 18, 2023)
17-28365162-A-G		not specified	Likely benign (Dec 12, 2023)
17-28365177-G-A		not specified	Uncertain significance (Apr 19, 2023)
17-28365227-C-T		not specified	Uncertain significance (Dec 06, 2023)
17-28367362-C-CT		VTN-related disorder	Likely benign (Nov 03, 2023)
17-28367411-G-A			Likely benign (Feb 09, 2018)
17-28367424-T-C		VTN-related disorder	Uncertain significance (Oct 20, 2022)
17-28367431-G-A		not specified	Uncertain significance (Aug 02, 2021)
17-28367440-T-C		not specified	Likely benign (May 23, 2023)
17-28367455-T-A		not specified	Uncertain significance (Sep 06, 2022)
17-28367462-A-G		VTN-related disorder	Benign (Nov 08, 2019)
17-28367725-G-T		not specified	Uncertain significance (May 23, 2023)
17-28367772-C-T		not specified	Uncertain significance (Jul 14, 2021)
17-28367777-C-T		not specified	Uncertain significance (Nov 17, 2023)
17-28367840-G-A		VTN-related disorder	Benign (Oct 30, 2019)
17-28367843-G-A		not specified	Uncertain significance (Aug 17, 2022)
17-28367844-C-T		not specified	Uncertain significance (Jan 18, 2022)
17-28367856-G-A		not specified	Uncertain significance (Feb 27, 2023)
17-28367869-G-A			Benign (Dec 31, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SARM1	protein_coding	protein_coding	ENST00000457710	9	36688

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.70e-10	0.380	5545	120044	4	125593	0.790

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.90	269	372	0.722	0.0000226	4301
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	4.00	2.68
Ashkenazi Jewish	2.00	0.794
East Asian	2.00	0.834
Finnish	2.00	0.817
European (Non-Finnish)	2.00	0.794
Middle Eastern	2.00	0.834
South Asian	2.00	0.771
Other	2.00	0.806

dbNSFP

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}.
• Pathway: Regulation of toll-like receptor signaling pathway;Toll Like Receptor 3 (TLR3) Cascade;Toll-Like Receptors Cascades;Innate Immune System;Immune System;Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon;IKK complex recruitment mediated by RIP1;TRAF6-mediated induction of TAK1 complex within TLR4 complex;TRIF(TICAM1)-mediated TLR4 signaling ;MyD88-independent TLR4 cascade ;Toll Like Receptor 4 (TLR4) Cascade (Consensus)

Recessive Scores

• pRec: 0.125

Haploinsufficiency Scores

• pHI: 0.198
• hipred: N
• hipred_score: 0.439
• ghis: 0.540

Essentials

• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.779

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Sarm1
• Phenotype: immune system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• 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;innate immune response;response to axon injury;regulation of dendrite morphogenesis;regulation of neuron death
• Cellular component: cytoplasm;mitochondrion;cytosol;microtubule;cell junction;axon;dendrite;extrinsic component of mitochondrial outer membrane;synapse
• Molecular function: protein binding;signaling adaptor activity