SSR4

signal sequence receptor subunit 4

Basic information

Region (hg38): X:153793516-153798499

Links

ENSG00000180879 ∙ NCBI:6748 ∙ OMIM:300090 ∙ HGNC:11326 ∙ Uniprot:P51571 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• SSR4-congenital disorder of glycosylation (Strong), mode of inheritance: XL
• SSR4-congenital disorder of glycosylation (Supportive), mode of inheritance: XL
• SSR4-congenital disorder of glycosylation (Moderate), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Congenital disorder of glycosylation, type Iy	XL	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Craniofacial; Musculoskeletal; Neurologic	24218363; 26264460
Hepatic-metabolized agents should be avoided

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SSR4 gene.

• SSR4-congenital disorder of glycosylation (2 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SSR4 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				14	1	15
missense			29			29
nonsense	2	1				3
start loss						0
frameshift	1					1
inframe indel				1		1
splice donor/acceptor (+/-2bp)		1	1	1		3
splice region			1	3		4
non coding			2	10	7	19
Total	3	2	32	26	8

Variants in SSR4

This is a list of pathogenic ClinVar variants found in the SSR4 region.

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

Position	Type	Phenotype	Significance	ClinVar
X-153794101-G-A			Benign (Jun 29, 2018)
X-153794290-C-G		not specified	Uncertain significance (Nov 02, 2023)
X-153794541-A-C		not specified	Benign (Jul 07, 2017)
X-153794580-C-G			Uncertain significance (Sep 08, 2017)
X-153794596-G-C			Likely benign (Nov 27, 2023)
X-153794634-G-GCCCCTCGTGTTCATGGGAGCTCGTTTT		not specified	Likely benign (Jul 20, 2016)
X-153794653-G-A		not specified	Likely benign (Jul 21, 2016)
X-153794656-C-G			Likely benign (Dec 14, 2023)
X-153794662-C-T			Likely benign (Jul 29, 2023)
X-153794663-T-C			Likely benign (Jan 24, 2024)
X-153794667-C-T		SSR4-related disorder	Benign (Nov 19, 2023)
X-153794674-G-T		SSR4-related disorder	Uncertain significance (Jan 04, 2023)
X-153794683-A-AGGCGATGGC			Likely benign (Dec 05, 2023)
X-153794719-C-T		Inborn genetic diseases	Uncertain significance (Apr 12, 2022)
X-153794726-C-G		SSR4-related disorder	Likely benign (Aug 28, 2019)
X-153794756-T-C		Inborn genetic diseases	Uncertain significance (Dec 29, 2021)
X-153796101-G-C			Benign (Jul 27, 2018)
X-153796262-T-C			Likely benign (Mar 29, 2020)
X-153796320-A-G			Benign (Jun 29, 2018)
X-153796423-C-T			Likely benign (Oct 13, 2023)
X-153796429-C-T		not specified	Likely benign (Dec 02, 2021)
X-153796430-G-A			Likely benign (Jan 21, 2024)
X-153796436-G-A		Inborn genetic diseases	Uncertain significance (Apr 22, 2022)
X-153796445-C-T			Likely benign (Dec 11, 2023)
X-153796446-T-C		Inborn genetic diseases	Uncertain significance (Nov 21, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SSR4	protein_coding	protein_coding	ENST00000320857	6	4990

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.875	0.124	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.902	55	77.3	0.711	0.00000645	1119
Missense in Polyphen		15	30.234	0.49613		458
Synonymous	-1.18	45	36.0	1.25	0.00000345	349
Loss of Function	2.41	0	6.78	0.00	4.86e-7	105

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: TRAP proteins are part of a complex whose function is to bind calcium to the ER membrane and thereby regulate the retention of ER resident proteins.
• Disease: DISEASE: Congenital disorder of glycosylation 1Y (CDG1Y) [MIM:300934]: A form of congenital disorder of glycosylation, a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. {ECO:0000269|PubMed:24218363}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Protein processing in endoplasmic reticulum - Homo sapiens (human);SRP-dependent cotranslational protein targeting to membrane;Translation;Metabolism of proteins (Consensus)

Recessive Scores

• pRec: 0.446

Intolerance Scores

• rvis_EVS: 0.01
• rvis_percentile_EVS: 54.63

Haploinsufficiency Scores

• pHI: 0.386
• hipred: Y
• hipred_score: 0.806
• ghis: 0.495

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.801

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ssr4

Zebrafish Information Network

• Gene name: ssr4
• Affected structure: post-vent region
• Phenotype tag: abnormal
• Phenotype quality: curved

Gene ontology

• Cellular component: Sec61 translocon complex;integral component of membrane;extracellular exosome