SERPINF1

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

Basic information

Region (hg38): 17:1762028-1777565

Previous symbols: [ "PEDF" ]

Links

ENSG00000132386 ∙ NCBI:5176 ∙ OMIM:172860 ∙ HGNC:8824 ∙ Uniprot:P36955 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• osteogenesis imperfecta type 6 (Strong), mode of inheritance: AR
• osteogenesis imperfecta type 6 (Strong), mode of inheritance: AR
• osteogenesis imperfecta type 3 (Supportive), mode of inheritance: AD
• osteogenesis imperfecta type 4 (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Osteogenesis imperfecta, type VI	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	Musculoskeletal	11771667; 17127117; 21353196; 21826736; 22947550; 23613367
Bisphosphonates may reduce fracture frequency, and use of RANKL antibody has been described as potentially beneficial

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SERPINF1 gene.

• not provided (233 variants)
• Osteogenesis imperfecta type 6 (70 variants)
• Osteogenesis imperfecta (24 variants)
• Inborn genetic diseases (22 variants)
• not specified (15 variants)
• Osteogenesis Imperfecta, Recessive (3 variants)
• Osteogenesis imperfecta type III (3 variants)
• Osteoporosis (1 variants)
• Abnormality of the skeletal system (1 variants)
• Hirschsprung disease, susceptibility to, 1 (1 variants)
• See cases (1 variants)
• SERPINF1-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SERPINF1 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			4	47	4	55
missense		1	92	2	4	99
nonsense	7	5	1			13
start loss						0
frameshift	13	3	2			18
inframe indel	1	1	4			6
splice donor/acceptor (+/-2bp)	1	3	1			5
splice region	1		5	5		11
non coding		2	4	34	29	69
Total	22	15	108	83	37

Highest pathogenic variant AF is 0.0000722

Variants in SERPINF1

This is a list of pathogenic ClinVar variants found in the SERPINF1 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-1762036-C-A		Osteogenesis Imperfecta, Recessive • Osteogenesis imperfecta	Benign/Likely benign (Aug 09, 2021)
17-1762085-C-A		Osteogenesis imperfecta type 6	Uncertain significance (Jul 23, 2020)
17-1762114-G-GT		Osteogenesis imperfecta type 6	Pathogenic (Oct 01, 2012)
17-1762119-G-A		Osteogenesis imperfecta	Uncertain significance (Mar 02, 2021)
17-1762130-G-A		not specified	Benign (Jun 09, 2017)
17-1762309-G-A			Benign (May 14, 2021)
17-1766648-AG-A			Likely benign (Jun 29, 2020)
17-1766736-G-T			Likely benign (Oct 05, 2018)
17-1766914-C-T		Osteogenesis imperfecta type 6	Likely pathogenic (Mar 17, 2024)
17-1766916-G-A			Likely benign (Apr 08, 2022)
17-1766925-G-T		Osteogenesis imperfecta type 6 • Osteogenesis imperfecta	Conflicting classifications of pathogenicity (Jan 25, 2024)
17-1766928-A-G			Likely benign (Oct 18, 2022)
17-1766931-C-A			Likely benign (Oct 18, 2022)
17-1766939-T-A		Inborn genetic diseases	Uncertain significance (Jan 29, 2024)
17-1766939-T-C		Inborn genetic diseases	Conflicting classifications of pathogenicity (May 15, 2023)
17-1766952-C-T		Osteogenesis imperfecta type 6	Conflicting classifications of pathogenicity (Nov 29, 2023)
17-1766953-G-A		Inborn genetic diseases	Uncertain significance (Nov 29, 2023)
17-1766955-G-C			Likely benign (May 09, 2022)
17-1766972-A-C			Uncertain significance (Aug 16, 2022)
17-1766981-G-A			Uncertain significance (Sep 19, 2022)
17-1766981-GC-G		Osteogenesis imperfecta type 6	Pathogenic (Jan 24, 2024)
17-1766981-G-GC		Osteogenesis imperfecta type 6	Pathogenic (Sep 27, 2021)
17-1766982-C-T			Likely benign (Oct 06, 2023)
17-1766983-C-A		Inborn genetic diseases	Uncertain significance (Mar 20, 2023)
17-1766987-C-G		SERPINF1-related disorder	Uncertain significance (Feb 21, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SERPINF1	protein_coding	protein_coding	ENST00000254722	7	15616

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.80e-8	0.489	125713	0	34	125747	0.000135

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.911	275	236	1.17	0.0000142	2714
Missense in Polyphen		88	80.507	1.0931		931
Synonymous	-2.31	136	106	1.29	0.00000699	866
Loss of Function	0.904	13	17.0	0.764	9.51e-7	197

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000362	0.000362
Ashkenazi Jewish	0.00	0.00
East Asian	0.000272	0.000272
Finnish	0.00	0.00
European (Non-Finnish)	0.000158	0.000158
Middle Eastern	0.000272	0.000272
South Asian	0.0000653	0.0000653
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Neurotrophic protein; induces extensive neuronal differentiation in retinoblastoma cells. Potent inhibitor of angiogenesis. As it does not undergo the S (stressed) to R (relaxed) conformational transition characteristic of active serpins, it exhibits no serine protease inhibitory activity. {ECO:0000269|PubMed:7592790, ECO:0000269|PubMed:8226833}.
• Disease: DISEASE: Osteogenesis imperfecta 6 (OI6) [MIM:613982]: 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. OI6 is a severe, autosomal recessive form compatible with OI type III in the Sillence classification. {ECO:0000269|PubMed:21353196}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Wnt signaling pathway - Homo sapiens (human);Wnt Signaling Pathway (Consensus)

Intolerance Scores

• loftool: 0.283
• rvis_EVS: -0.6
• rvis_percentile_EVS: 18.19

Haploinsufficiency Scores

• pHI: 0.458
• hipred: N
• hipred_score: 0.219
• ghis: 0.594

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.152

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Serpinf1
• Phenotype: reproductive system 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); hematopoietic system phenotype; pigmentation 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); digestive/alimentary phenotype; vision/eye phenotype; immune system phenotype; skeleton phenotype; endocrine/exocrine gland phenotype

Gene ontology

• Biological process: kidney development;multicellular organism development;aging;short-term memory;cell population proliferation;response to acidic pH;negative regulation of endothelial cell migration;negative regulation of gene expression;negative regulation of endopeptidase activity;positive regulation of neuron projection development;negative regulation of angiogenesis;ovulation cycle;response to arsenic-containing substance;negative regulation of inflammatory response;positive regulation of neurogenesis;retina development in camera-type eye;negative regulation of epithelial cell proliferation involved in prostate gland development;cellular response to cobalt ion;cellular response to retinoic acid;cellular response to glucose stimulus;cellular response to dexamethasone stimulus;negative regulation of neuron death
• Cellular component: extracellular region;basement membrane;extracellular space;melanosome;axon hillock;perinuclear region of cytoplasm;collagen-containing extracellular matrix;extracellular exosome
• Molecular function: serine-type endopeptidase inhibitor activity;protein binding