SEC61A1

SEC61 translocon subunit alpha 1

Basic information

Region (hg38): 3:128051641-128071705

Links

ENSG00000058262 ∙ NCBI:29927 ∙ OMIM:609213 ∙ HGNC:18276 ∙ Uniprot:P61619 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hyperuricemic nephropathy, familial juvenile type 4 (Strong), mode of inheritance: AD
• SEC61A1 deficiency (Moderate), mode of inheritance: AD
• hyperuricemic nephropathy, familial juvenile type 4 (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency, common variable, 15; Neutropenia, severe congenital, 11, autosomal dominant; Tubulointerstitial kidney disease, autosomal dominant, 5	AD	Allergy/Immunology/Infectious; Renal	Immunodeficiency, common variable, 15 involves an increased risk of infections, and awareness may allow preventative measures (eg, treatment with IVIG) and early and aggressive treatment of infections; Neutropenia, severe congenital, 11, autosomal dominant may involve increased risk of infections, and preventative measures and medical management (eg, with G-CSF) as well as early and aggressive treatment of infections, has been reported as beneficial; Individuals with Tubulointerstitial kidney disease, autosomal dominant, 5 may have anemia, and medical management (with erythropoietin) has been described as beneficial; The hyperuricemic nephropathy may manifest with a number of variable renal sequelae, and early awareness may allow prompt medical management	Allergy/Immunology/Infectious; Hematologic; Renal	27392076; 28782633; 32325141

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SEC61A1 gene.

• Hyperuricemic nephropathy, familial juvenile type 4 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SEC61A1 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				66	5	71
missense	1	3	74	1		79
nonsense						0
start loss						0
frameshift						0
inframe indel			1			1
splice donor/acceptor (+/-2bp)			2		1	3
splice region			14	18	4	36
non coding			3	46	21	70
Total	1	3	80	113	27

Variants in SEC61A1

This is a list of pathogenic ClinVar variants found in the SEC61A1 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-128051906-G-A			Likely benign (May 01, 2024)
3-128052146-C-G			Likely benign (Jun 07, 2021)
3-128052158-A-G			Likely benign (Oct 03, 2021)
3-128052316-G-A			Benign (Sep 02, 2019)
3-128052569-G-A			Likely benign (Jul 06, 2022)
3-128052577-G-T			Likely benign (Nov 01, 2022)
3-128052579-C-A			Likely benign (Mar 12, 2023)
3-128052796-T-A			Likely benign (Mar 04, 2021)
3-128052818-T-C			Likely benign (Jun 08, 2022)
3-128052823-C-T			Likely benign (Jun 24, 2023)
3-128052826-C-T			Likely benign (Oct 19, 2022)
3-128052830-C-G			Likely benign (Nov 06, 2023)
3-128052831-A-G			Likely benign (Jun 10, 2022)
3-128052843-C-T			Likely benign (Dec 27, 2023)
3-128052858-C-T			Uncertain significance (Mar 08, 2023)
3-128052860-C-T			Likely benign (Dec 02, 2022)
3-128052896-G-A			Likely benign (Mar 19, 2022)
3-128052905-A-G			Uncertain significance (Jul 17, 2023)
3-128052907-G-A			Uncertain significance (Feb 08, 2022)
3-128052909-A-T			Likely benign (Dec 09, 2024)
3-128052909-AC-A			Benign (Apr 19, 2023)
3-128052913-C-T			Likely benign (Jan 11, 2025)
3-128052915-A-C			Likely benign (Nov 19, 2023)
3-128052921-CAACA-C			Likely benign (Dec 29, 2024)
3-128055502-C-A			Likely benign (Jan 04, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SEC61A1	protein_coding	protein_coding	ENST00000243253	12	20043

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.987	0.0133	125739	0	9	125748	0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.06	92	285	0.323	0.0000162	3081
Missense in Polyphen		16	89.878	0.17802		958
Synonymous	-0.297	118	114	1.04	0.00000690	988
Loss of Function	4.21	3	26.3	0.114	0.00000154	276

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000118	0.000118
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000352	0.0000352
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of SEC61 channel-forming translocon complex that mediates transport of signal peptide-containing precursor polypeptides across endoplasmic reticulum (ER). Forms a ribosome receptor and a gated pore in the ER membrane, both functions required for cotranslational translocation of signal peptide- containing precursor proteins (PubMed:22375059, PubMed:28782633, PubMed:29719251). May cooperate with auxiliary protein SEC62, SEC63 and HSPA5/BiP to enable post-translational transport of small presecretory proteins (PubMed:22375059, PubMed:29719251). Controls the passive efflux of calcium ions from the ER lumen to the cytosol through SEC61 channel, contributing to the maintenance of cellular calcium homeostasis (PubMed:28782633). Plays a critical role in nephrogenesis, specifically at pronephros stage (By similarity). {ECO:0000250|UniProtKB:P61620, ECO:0000269|PubMed:22375059, ECO:0000269|PubMed:28782633, ECO:0000269|PubMed:29719251}.
• Disease: DISEASE: Note=Defects in SEC61A1 may be a cause of autosomal dominant hypogammaglobulinemia, resulting in severe recurrent infections, mainly of the respiratory tract. Disease onset is mostly in the first year of life. Affected subjects manifest reduced antibodies production by plasma cells, in the presence of normal subpopulations of B and T cells in the peripheral blood. Patients respond well to immunoglobulin replacement therapy. {ECO:0000269|PubMed:28782633}.
• Pathway: Protein export - Homo sapiens (human);Phagosome - Homo sapiens (human);Protein processing in endoplasmic reticulum - Homo sapiens (human);Vibrio cholerae infection - Homo sapiens (human);XBP1(S) activates chaperone genes;SRP-dependent cotranslational protein targeting to membrane;er associated degradation (erad) pathway;IRE1alpha activates chaperones;Unfolded Protein Response (UPR);Translation;Metabolism of proteins;Immune System;Adaptive Immune System;Antigen processing-Cross presentation;Class I MHC mediated antigen processing & presentation;ER-Phagosome pathway (Consensus)

Recessive Scores

• pRec: 0.400

Intolerance Scores

• loftool: 0.0358
• rvis_EVS: -0.54
• rvis_percentile_EVS: 20.26

Haploinsufficiency Scores

• pHI: 0.860
• hipred: Y
• hipred_score: 0.786
• ghis: 0.644

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.867

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Sec61a1
• Phenotype: liver/biliary system phenotype; cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype

Zebrafish Information Network

• Gene name: sec61a1l
• Affected structure: pronephric tubule
• Phenotype tag: abnormal
• Phenotype quality: atrophied

Gene ontology

• Biological process: cotranslational protein targeting to membrane;SRP-dependent cotranslational protein targeting to membrane;SRP-dependent cotranslational protein targeting to membrane, translocation;posttranslational protein targeting to endoplasmic reticulum membrane;endoplasmic reticulum organization;response to interferon-gamma;pronephric nephron development;protein targeting to ER
• Cellular component: endoplasmic reticulum;Sec61 translocon complex;endoplasmic reticulum membrane;cytosol;membrane;integral component of endoplasmic reticulum membrane
• Molecular function: signal sequence binding;protein binding;protein transmembrane transporter activity;ribosome binding