SYNM

protein-coding

synemin, the group of Intermediate filaments Type IV|A-kinase anchoring proteins

Gene summary

The protein encoded by this gene is an intermediate filament (IF) family member. IF proteins are cytoskeletal proteins that confer resistance to mechanical stress and are encoded by a dispersed multigene family. This protein has been found to form a linkage between desmin, which is a subunit of the IF network, and the extracellular matrix, and provides an important structural support in muscle. Two alternatively spliced variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

Previous symbols:

MANE transcript

NM_145728.3

Inheritance

—

ClinVar variants

U:125B:95

Top phenotype

SYNM-related disorder

gnomAD constraint

pLI —, LoF o/e 0.89

Max pathogenic AF

—

Genomic locus

chr15:99,098,217-99,135,593

External References & Databases

Ensembl (ENSG00000182253)

Transcript & Mutation Effects

hg38 • Region Span ~37.4 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 SYNM variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 131

SYNM-related disorderTotal: 49

not providedTotal: 44

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_145728.3. 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	24 clinvar	18 clinvar	44
missense			122 clinvar	28 clinvar	22 clinvar	172
nonsense				1 clinvar	1 clinvar	2
start loss						0
frameshift					1 clinvar	1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	125	53	42	220

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_145728.3	RefSeq	NP_663780.2	4	MANE Select
ENST00000336292.11	Ensembl	ENSP00000336775.7	4	MANE Select
NM_015286.6	RefSeq	NP_056101.5	5	Standard
ENST00000328642.11	Ensembl	ENSP00000330469.8	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

fast-twitch skeletal muscle fiber contraction
intermediate filament cytoskeleton organization

Molecular Function

structural constituent of cytoskeleton
protein binding
structural constituent of muscle
vinculin binding
intermediate filament binding

Cellular Component

intermediate filament
adherens junction
sarcolemma
costamere
neurofilament cytoskeleton

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000336292
Coding exons: 5
Length: 37379
Individuals with no LoFs: 124136
Homozygous LoFs: 2
Heterozygous LoFs: 571
Defined: 124709
p: 0.00230

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.673	862	808	1.07	0.0000487	9932
Missense (PolyPhen)		212	220.73	0.96043		3031
Synonymous	-1.07	376	351	1.07	0.0000245	3219
Loss of Function	0.680	39	43.9	0.889	0.00000239	551

Population LoF Frequency

Population	CAF	p-value	Status
African	0.017	0.014	notable
Latino/Admixed American	0.0020	0.0017	notable
Ashkenazi Jewish	0.0040	0.0040	notable
East Asian	0.00068	0.00067	rare
Finnish	0.0016	0.0016	notable
European (Non-Finnish)	0.0012	0.0011	notable
South Asian	0.0024	0.0024	notable
Other	0.0023	0.0023	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Type-VI intermediate filament (IF) which plays an important cytoskeletal role within the muscle cell cytoskeleton. It forms heteropolymeric IFs with desmin and/or vimentin, and via its interaction with cytoskeletal proteins alpha-dystrobrevin, dystrophin, talin-1, utrophin and vinculin, is able to link these heteropolymeric IFs to adherens-type junctions, such as to the costameres, neuromuscular junctions, and myotendinous junctions within striated muscle cells. {ECO:0000269|PubMed:11353857, ECO:0000269|PubMed:16777071, ECO:0000269|PubMed:18028034}.;

Recessive Scores

pRec: 0.359

Essentials

Essential (CRISPR2): N
Indispensability pred.: E
Indispensability score: 0.787

Gene Damage Prediction

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