UFSP2

UFM1 specific peptidase 2

Basic information

Region (hg38): 4:185399537-185425979

Previous symbols: [ "C4orf20" ]

Links

ENSG00000109775 ∙ NCBI:55325 ∙ OMIM:611482 ∙ HGNC:25640 ∙ Uniprot:Q9NUQ7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hip dysplasia, Beukes type (Limited), mode of inheritance: AD
• hip dysplasia, Beukes type (Supportive), mode of inheritance: AD
• autosomal recessive non-syndromic intellectual disability (Supportive), mode of inheritance: AR
• developmental and epileptic encephalopathy 106 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hip dysplasia, Beukes type; Spondyloepimetaphyseal dysplasia, Di Rocco type	AD	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	2389793; 28892125

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the UFSP2 gene.

• Hip dysplasia, Beukes type (1 variants)
• Spondyloepimetaphyseal dysplasia, di rocco type (1 variants)
• Developmental and epileptic encephalopathy 106 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the UFSP2 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	5	7
missense	1	2	21	3	1	28
nonsense						0
start loss						0
frameshift	1		1			2
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			4		2	6
Total	2	2	26	5	8

Highest pathogenic variant AF is 0.0000460

Variants in UFSP2

This is a list of pathogenic ClinVar variants found in the UFSP2 region.

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

Position	Type	Phenotype	Significance	ClinVar
4-185399586-G-A		not specified	Uncertain significance (Nov 07, 2022)
4-185399611-G-C		not specified	Uncertain significance (Jun 12, 2023)
4-185399661-A-G		not specified	Uncertain significance (Nov 19, 2022)
4-185399712-G-A		not specified	Uncertain significance (Apr 17, 2024)
4-185400426-T-G			Uncertain significance (Dec 17, 2022)
4-185400429-T-C		Cerebral visual impairment and intellectual disability	Likely pathogenic (Sep 09, 2015)
4-185400462-T-G		not specified	Uncertain significance (Apr 07, 2022)
4-185400469-C-T		Hip dysplasia, Beukes type	Uncertain significance (Mar 29, 2024)
4-185403521-A-G			Benign (Dec 31, 2019)
4-185403526-C-G			Uncertain significance (-)
4-185403534-T-C		Spondyloepimetaphyseal dysplasia, di rocco type	Likely pathogenic (Feb 23, 2024)
4-185403540-T-G		Hip dysplasia, Beukes type • Spondyloepimetaphyseal dysplasia, di rocco type	Pathogenic (Oct 15, 2018)
4-185403591-A-G		not specified	Uncertain significance (Oct 27, 2023)
4-185403612-C-T		not specified	Uncertain significance (Jun 13, 2024)
4-185405797-C-T		not specified	Uncertain significance (Dec 20, 2021)
4-185405828-G-A		not specified	Uncertain significance (Jun 23, 2023)
4-185408014-C-T		not specified	Uncertain significance (Mar 31, 2024)
4-185408021-C-T			Uncertain significance (Jan 01, 2023)
4-185408022-G-A		UFSP2-related disorder	Likely benign (Feb 22, 2019)
4-185408031-T-C		UFSP2-related disorder	Likely benign (Mar 12, 2019)
4-185408045-C-T		Developmental and epileptic encephalopathy 106	Uncertain significance (Mar 07, 2023)
4-185408054-C-T		not specified	Uncertain significance (Dec 17, 2023)
4-185408060-C-T		UFSP2-related disorder	Likely benign (Dec 27, 2022)
4-185408304-C-T			Benign (Dec 31, 2019)
4-185408335-C-G		Hip dysplasia, Beukes type;Spondyloepimetaphyseal dysplasia, di rocco type	Benign/Likely benign (Aug 06, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
UFSP2	protein_coding	protein_coding	ENST00000264689	12	26446

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000306	0.985	125686	0	62	125748	0.000247

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.476	235	256	0.916	0.0000131	3070
Missense in Polyphen		58	80.236	0.72287		923
Synonymous	-0.124	93	91.5	1.02	0.00000501	884
Loss of Function	2.22	13	25.0	0.521	0.00000112	322

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00111	0.00111
Ashkenazi Jewish	0.000207	0.000198
East Asian	0.000287	0.000272
Finnish	0.00	0.00
European (Non-Finnish)	0.000258	0.000255
Middle Eastern	0.000287	0.000272
South Asian	0.000142	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Thiol protease which recognizes and hydrolyzes the peptide bond at the C-terminal Gly of UFM1, a ubiquitin-like modifier protein bound to a number of target proteins. Does not hydrolyze SUMO1 or ISG15 ubiquitin-like proteins. Through TRIP4 deufmylation may regulate intracellular nuclear receptors transactivation and thereby regulate cell proliferation and differentiation. {ECO:0000269|PubMed:25219498}.
• Disease: DISEASE: Beukes familial hip dysplasia (BFHD) [MIM:142669]: A severe progressive degenerative osteoarthritis of the hip joint with underlying dysplasia confined to that region. Affected individuals are of normal stature and have no associated health problems. {ECO:0000269|PubMed:26428751, ECO:0000269|PubMed:28892125}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.107

Intolerance Scores

• loftool: 0.818
• rvis_EVS: -0.03
• rvis_percentile_EVS: 51.92

Haploinsufficiency Scores

• pHI: 0.228
• hipred: N
• hipred_score: 0.229
• ghis: 0.547

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.690

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ufsp2

Gene ontology

• Biological process: proteolysis;regulation of intracellular estrogen receptor signaling pathway
• Cellular component: nucleus;cytoplasm;endoplasmic reticulum
• Molecular function: protein binding;thiolester hydrolase activity;UFM1 hydrolase activity