SEM1

SEM1 26S proteasome subunit, the group of Proteasome|Transcription and export complex 2

Basic information

Region (hg38): 7:96481626-96709880

Previous symbols: [ "SHFD1", "SHFM1", "C7orf76" ]

Links

ENSG00000127922 ∙ NCBI:7979 ∙ OMIM:601285 ∙ HGNC:10845 ∙ Uniprot:P60896, Q6ZVN7 ∙ 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 SEM1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SEM1 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				2		2
missense			2			2
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	2	2	0

Variants in SEM1

This is a list of pathogenic ClinVar variants found in the SEM1 region.

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

Position	Type	Phenotype	Significance	ClinVar
7-96486350-C-G		SEM1-related disorder	Uncertain significance (Jul 16, 2023)
7-96688954-C-T			Likely benign (Apr 13, 2018)
7-96694879-A-G		not specified	Uncertain significance (Jan 31, 2022)
7-96709693-G-A		not specified	Uncertain significance (Nov 06, 2023)
7-96709731-A-T			Likely benign (May 18, 2018)
7-96709732-C-T		not specified	Uncertain significance (Nov 10, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SEM1	protein_coding	protein_coding	ENST00000248566	3	228266

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.763	0.229	125260	0	1	125261	0.00000399

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.546	27	36.2	0.745	0.00000162	469
Missense in Polyphen		14	21.108	0.66325		296
Synonymous	-0.850	17	13.1	1.30	5.94e-7	101
Loss of Function	2.02	0	4.76	0.00	2.02e-7	55

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)	0.00000883	0.00000883
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair (PubMed:15117943). Component of the TREX-2 complex (transcription and export complex 2), composed of at least ENY2, GANP, PCID2, SEM1, and either centrin CETN2 or CETN3 (PubMed:22307388). The TREX-2 complex functions in docking export-competent ribonucleoprotein particles (mRNPs) to the nuclear entrance of the nuclear pore complex (nuclear basket). TREX-2 participates in mRNA export and accurate chromatin positioning in the nucleus by tethering genes to the nuclear periphery. Binds and stabilizes BRCA2 and is thus involved in the control of R-loop-associated DNA damage and thus transcription-associated genomic instability. R-loop accumulation increases in SEM1-depleted cells. {ECO:0000269|PubMed:1317798, ECO:0000269|PubMed:15117943, ECO:0000269|PubMed:22307388, ECO:0000269|PubMed:24896180}.
• Pathway: Homologous recombination - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);Proteasome - Homo sapiens (human);Post-translational protein modification;Metabolism of proteins;UCH proteinases;Neddylation;Ub-specific processing proteases;Deubiquitination (Consensus)

Recessive Scores

• pRec: 0.240

Intolerance Scores

• rvis_EVS: 0.01
• rvis_percentile_EVS: 54.63

Haploinsufficiency Scores

• pHI: 0.401
• hipred: Y
• hipred_score: 0.757
• ghis: 0.652

Essentials

• essential_gene_gene_trap: E

Mouse Genome Informatics

• Gene name: Sem1

Gene ontology

• Biological process: double-strand break repair via homologous recombination