RSPRY1

ring finger and SPRY domain containing 1, the group of Ring finger proteins

Basic information

Region (hg38): 16:57186137-57240469

Links

ENSG00000159579 ∙ NCBI:89970 ∙ OMIM:616585 ∙ HGNC:29420 ∙ Uniprot:Q96DX4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• progressive spondyloepimetaphyseal dysplasia-short stature-short fourth metatarsals-intellectual disability syndrome (Strong), mode of inheritance: AR
• progressive spondyloepimetaphyseal dysplasia-short stature-short fourth metatarsals-intellectual disability syndrome (Supportive), mode of inheritance: AR
• progressive spondyloepimetaphyseal dysplasia-short stature-short fourth metatarsals-intellectual disability syndrome (Moderate), mode of inheritance: AR
• progressive spondyloepimetaphyseal dysplasia-short stature-short fourth metatarsals-intellectual disability syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spondyloepimetaphyseal dysplasia, Faden-Alkuraya type	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; Musculoskeletal; Neurologic	26365341

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RSPRY1 gene.

• not_provided (135 variants)
• Inborn_genetic_diseases (42 variants)
• Progressive_spondyloepimetaphyseal_dysplasia-short_stature-short_fourth_metatarsals-intellectual_disability_syndrome (11 variants)
• RSPRY1-related_disorder (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RSPRY1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000133368.3. 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				47	5	52
missense	1		58	1	1	61
nonsense	2					2
start loss						0
frameshift	1	2				3
splice donor/acceptor (+/-2bp)		1				1
Total	4	3	58	48	6

Highest pathogenic variant AF is 0.0000047883746

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RSPRY1	protein_coding	protein_coding	ENST00000537866	14	54339

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000185	125740	0	8	125748	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.36	150	319	0.470	0.0000169	3790
Missense in Polyphen		43	143.77	0.29909		1675
Synonymous	1.26	101	118	0.853	0.00000640	1091
Loss of Function	5.03	2	33.3	0.0600	0.00000174	383

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000904	0.0000904
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000528	0.0000527
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Disease: DISEASE: Spondyloepimetaphyseal dysplasia, Faden-Alkuraya type (SEMDFA) [MIM:616723]: An autosomal recessive skeletal disorder characterized by spondyloepimetaphyseal dysplasia, short stature, facial dysmorphism, short fourth metatarsals, and intellectual disability. {ECO:0000269|PubMed:26365341}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Intolerance Scores

• loftool: 0.148
• rvis_EVS: -0.29
• rvis_percentile_EVS: 32.94

Haploinsufficiency Scores

• pHI: 0.396
• hipred: Y
• hipred_score: 0.673
• ghis: 0.648

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.811

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rspry1

Gene ontology

• Cellular component: extracellular region
• Molecular function: metal ion binding