SERPINH1

serpin family H member 1, the group of Serpin peptidase inhibitors

Basic information

Region (hg38): 11:75562055-75572783

Previous symbols: [ "CBP1", "CBP2", "SERPINH2" ]

Links

ENSG00000149257 ∙ NCBI:871 ∙ OMIM:600943 ∙ HGNC:1546 ∙ Uniprot:P50454 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• osteogenesis imperfecta type 3 (Supportive), mode of inheritance: AD
• osteogenesis imperfecta type 10 (Moderate), mode of inheritance: AR
• osteogenesis imperfecta type 10 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Osteogenesis imperfecta, type X	AR	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	Craniofacial; Dental; Musculoskeletal; Ophthalmologic; Renal	20188343

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SERPINH1 gene.

• not provided (150 variants)
• Osteogenesis imperfecta type 10 (61 variants)
• not specified (16 variants)
• Inborn genetic diseases (13 variants)
• Osteogenesis imperfecta (8 variants)
• Osteogenesis Imperfecta, Recessive (2 variants)
• Preterm premature rupture of membranes;Osteogenesis imperfecta type 10 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SERPINH1 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			6	33	6	45
missense			81	4		85
nonsense	1		1			2
start loss						0
frameshift			2			2
inframe indel			2			2
splice donor/acceptor (+/-2bp)						0
splice region			1	3	1	5
non coding			12	13	11	36
Total	1	0	104	50	17

Variants in SERPINH1

This is a list of pathogenic ClinVar variants found in the SERPINH1 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-75562085-CA-C		Osteogenesis Imperfecta, Recessive	Likely benign (Jun 14, 2016)
11-75562143-G-A		Osteogenesis imperfecta type 10	Uncertain significance (Jan 13, 2018)
11-75562163-A-G		Osteogenesis imperfecta type 10	Uncertain significance (Jan 13, 2018)
11-75562165-G-A		Osteogenesis imperfecta type 10	Benign (Jan 12, 2018)
11-75562169-T-C		Osteogenesis imperfecta type 10	Uncertain significance (Jan 13, 2018)
11-75562281-G-A		Osteogenesis imperfecta type 10	Benign (Jan 13, 2018)
11-75566213-G-A			Likely benign (Jun 16, 2018)
11-75566217-C-T			Likely benign (Jan 13, 2019)
11-75566331-C-T		Osteogenesis imperfecta type 10 • not specified	Benign (Jan 13, 2018)
11-75566376-C-T			Likely benign (Apr 10, 2018)
11-75566379-C-T			Likely benign (Jul 30, 2022)
11-75566395-G-T			Uncertain significance (Aug 23, 2022)
11-75566400-G-C			Likely benign (Aug 08, 2017)
11-75566403-C-T			Likely benign (Jun 13, 2022)
11-75566404-G-A			Uncertain significance (Aug 20, 2022)
11-75566407-G-A		Osteogenesis imperfecta type 10	Uncertain significance (Feb 02, 2018)
11-75566427-C-T			Likely benign (Aug 11, 2023)
11-75566428-G-GCAGCAGCTCCTGGCA			Uncertain significance (Sep 16, 2018)
11-75566436-T-A			Likely benign (Jul 11, 2022)
11-75566441-G-C		Osteogenesis imperfecta type 10 • SERPINH1-related disorder	Conflicting classifications of pathogenicity (Jan 19, 2024)
11-75566443-A-G			Uncertain significance (Jun 03, 2022)
11-75566444-C-T			Uncertain significance (Jul 07, 2022)
11-75566446-G-C			Conflicting classifications of pathogenicity (Dec 11, 2023)
11-75566449-G-A			Uncertain significance (Nov 05, 2021)
11-75566451-G-A			Likely benign (Nov 29, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SERPINH1	protein_coding	protein_coding	ENST00000524558	4	10728

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0276	0.962	125729	0	18	125747	0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0482	269	271	0.992	0.0000201	2699
Missense in Polyphen		88	103	0.85438		1116
Synonymous	-0.783	140	129	1.09	0.0000111	844
Loss of Function	2.25	5	14.1	0.355	8.01e-7	155

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000276	0.000266
Ashkenazi Jewish	0.000201	0.0000992
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000815	0.0000791
Middle Eastern	0.00	0.00
South Asian	0.0000987	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Binds specifically to collagen. Could be involved as a chaperone in the biosynthetic pathway of collagen.
• Disease: DISEASE: Osteogenesis imperfecta 10 (OI10) [MIM:613848]: A form of osteogenesis imperfecta, a connective tissue disorder characterized by low bone mass, bone fragility and susceptibility to fractures after minimal trauma. Disease severity ranges from very mild forms without fractures to intrauterine fractures and perinatal lethality. Extraskeletal manifestations, which affect a variable number of patients, are dentinogenesis imperfecta, hearing loss, and blue sclerae. OI10 is an autosomal recessive form characterized by multiple bone deformities and fractures, generalized osteopenia, dentinogenesis imperfecta, and blue sclerae. {ECO:0000269|PubMed:20188343}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Cellular response to heat stress;Endochondral Ossification;HSF1 activation;Attenuation phase;HSF1-dependent transactivation;Regulation of HSF1-mediated heat shock response;Collagen biosynthesis and modifying enzymes;Cellular responses to stress;Collagen formation;Extracellular matrix organization;Cellular responses to external stimuli;Cellular response to heat stress (Consensus)

Recessive Scores

• pRec: 0.396

Intolerance Scores

• loftool: 0.120
• rvis_EVS: -0.6
• rvis_percentile_EVS: 17.91

Haploinsufficiency Scores

• pHI: 0.840
• hipred: N
• hipred_score: 0.443
• ghis: 0.592

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.712

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Serpinh1
• Phenotype: skeleton phenotype; digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); respiratory system phenotype; embryo phenotype; craniofacial phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: serpinh1b
• Affected structure: regenerating fin
• Phenotype tag: abnormal
• Phenotype quality: decreased length

Gene ontology

• Biological process: chondrocyte development involved in endochondral bone morphogenesis;response to unfolded protein;negative regulation of endopeptidase activity;collagen fibril organization;collagen biosynthetic process;protein maturation
• Cellular component: extracellular space;endoplasmic reticulum;endoplasmic reticulum lumen;endoplasmic reticulum-Golgi intermediate compartment;membrane raft;collagen-containing extracellular matrix
• Molecular function: RNA binding;serine-type endopeptidase inhibitor activity;collagen binding;unfolded protein binding