STN1

STN1 subunit of CST complex, the group of CST complex

Basic information

Region (hg38): 10:103856806-103918332

Previous symbols: [ "OBFC1" ]

Links

ENSG00000107960 ∙ NCBI:79991 ∙ OMIM:613128 ∙ HGNC:26200 ∙ Uniprot:Q9H668 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Coats plus syndrome (Supportive), mode of inheritance: AR
• cerebroretinal microangiopathy with calcifications and cysts 2 (Moderate), mode of inheritance: AR
• cerebroretinal microangiopathy with calcifications and cysts 2 (Strong), mode of inheritance: AR
• cerebroretinal microangiopathy with calcifications and cysts 2 (Moderate), mode of inheritance: AR
• cerebroretinal microangiopathy with calcifications and cysts 2 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cerebroretinal microangiopathy with calcifications and cysts 2	AR	Cardiovascular; Gastrointestinal; Hematologic	Among other features, individuals have been described with gastrointestinal bleeding, and awareness may allow medical management (eg, with thalidomide treatment and argon plasma coagulation) as well as prompt treatment of urgent situations; RBC transfusions have been described as necessary due to bone marrow failure	Cardiovascular; Gastrointestinal; Hematologic; Neurologic; Ophthalmologic	27432940

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the STN1 gene.

• not_provided (244 variants)
• Inborn_genetic_diseases (54 variants)
• Cerebroretinal_microangiopathy_with_calcifications_and_cysts_2 (9 variants)
• STN1-related_disorder (8 variants)
• Brain_disorder (2 variants)
• not_specified (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the STN1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000024928.5. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				57	1	58
missense	1	1	122	9		133
nonsense			4			4
start loss						0
frameshift		1	7			8
splice donor/acceptor (+/-2bp)			6			6
Total	1	2	139	66	1

Highest pathogenic variant AF is 0.0000198366

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
STN1	protein_coding	protein_coding	ENST00000224950	9	35664

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.30e-10	0.254	125700	0	48	125748	0.000191

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.388	186	201	0.923	0.0000104	2436
Missense in Polyphen		39	56.526	0.68995		751
Synonymous	-0.0288	75	74.7	1.00	0.00000388	673
Loss of Function	0.778	17	20.8	0.816	0.00000115	236

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000333	0.000333
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.000247	0.000246
Middle Eastern	0.00	0.00
South Asian	0.000361	0.000359
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the CST complex proposed to act as a specialized replication factor promoting DNA replication under conditions of replication stress or natural replication barriers such as the telomere duplex. The CST complex binds single-stranded DNA with high affinity in a sequence-independent manner, while isolated subunits bind DNA with low affinity by themselves. Initially the CST complex has been proposed to protect telomeres from DNA degradation (PubMed:19854130). However, the CST complex has been shown to be involved in several aspects of telomere replication. The CST complex inhibits telomerase and is involved in telomere length homeostasis; it is proposed to bind to newly telomerase-synthesized 3' overhangs and to terminate telomerase action implicating the association with the ACD:POT1 complex thus interfering with its telomerase stimulation activity. The CST complex is also proposed to be involved in fill-in synthesis of the telomeric C-strand probably implicating recruitment and activation of DNA polymerase alpha (PubMed:22964711, PubMed:22763445). The CST complex facilitates recovery from many forms of exogenous DNA damage; seems to be involved in the re- initiation of DNA replication at repaired forks and/or dormant origins (PubMed:25483097). Required for efficicient replication of the duplex region of the telomere. Promotes efficient replication of lagging-strand telomeres (PubMed:22863775, PubMed:22964711). Promotes general replication start following replication-fork stalling implicating new origin firing (PubMed:22863775). May be in involved in C-strand fill-in during late S/G2 phase independent of its role in telomere duplex replication (PubMed:23142664). {ECO:0000269|PubMed:19648609, ECO:0000269|PubMed:19854130, ECO:0000269|PubMed:22763445, ECO:0000269|PubMed:22863775, ECO:0000269|PubMed:22964711, ECO:0000269|PubMed:23142664, ECO:0000269|PubMed:25483097, ECO:0000305|PubMed:23851344}.
• Disease: DISEASE: Cerebroretinal microangiopathy with calcifications and cysts 2 (CRMCC2) [MIM:617341]: An autosomal recessive, multisystemic disorder characterized by intrauterine growth retardation and, later in life, premature aging symptoms, including poor growth, graying hair, liver fibrosis, portal hypertension, esophageal varices, osteopenia, pancytopenia, hypocellular bone marrow, and vascular telangiectasia resulting in gastrointestinal bleeding. Brain calcifications and white matter changes are responsible for signs including spasticity, ataxia, or dystonia observed in some patients. {ECO:0000269|PubMed:27432940}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Lung fibrosis (Consensus)

Recessive Scores

• pRec: 0.0917

Intolerance Scores

• rvis_EVS: 0.35
• rvis_percentile_EVS: 74.37

Haploinsufficiency Scores

• pHI: 0.0608
• hipred: N
• hipred_score: 0.409
• ghis: 0.383

Essentials

• essential_gene_gene_trap: K

Mouse Genome Informatics

• Gene name: Stn1

Zebrafish Information Network

• Gene name: stn1
• Affected structure: pro-T cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: telomere maintenance;telomere maintenance via telomere lengthening;telomere capping;negative regulation of telomere maintenance via telomerase;positive regulation of DNA replication
• Cellular component: nuclear chromosome, telomeric region;fibrillar center;nucleus;nucleoplasm;intracellular membrane-bounded organelle;intermediate filament cytoskeleton;CST complex
• Molecular function: single-stranded DNA binding;protein binding;telomeric DNA binding;single-stranded telomeric DNA binding