SHPRH

protein-coding

SNF2 histone linker PHD RING helicase, the group of PHD finger proteins|Ring finger proteins

Gene summary

SHPRH is a ubiquitously expressed protein that contains motifs characteristics of several DNA repair proteins, transcription factors, and helicases. SHPRH is a functional homolog of S. cerevisiae RAD5 (Unk et al., 2006 [PubMed 17108083]).[supplied by OMIM, Mar 2008]

MANE transcript

NM_001042683.3

Inheritance

—

ClinVar variants

U:180B:8

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.31

Max pathogenic AF

—

Genomic locus

chr6:145,864,245-145,964,423

External References & Databases

Ensembl (ENSG00000146414)

Transcript & Mutation Effects

hg38 • Region Span ~100.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SHPRH variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 177

not providedTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001042683.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				2 clinvar		2
missense			178 clinvar	5 clinvar	1 clinvar	184
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	180	7	1	188

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 35 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001042683.3	RefSeq	NP_001036148.2	29	MANE Select
ENST00000275233.12	Ensembl	ENSP00000275233.7	29	MANE Select
NM_001370327.1	RefSeq	NP_001357256.1	29	Standard
NM_001370328.1	RefSeq	NP_001357257.1	24	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Post-translational protein modification
Metabolism of proteins
Protein ubiquitination
E3 ubiquitin ligases ubiquitinate target proteins

Biological Process

protein polyubiquitination
DNA repair
nucleosome assembly
cellular response to DNA damage stimulus
protein ubiquitination

Molecular Function

DNA binding
helicase activity
ubiquitin-protein transferase activity
protein binding
ATP binding

Cellular Component

nucleosome
nucleoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000367505
Coding exons: 29
Length: 100179
Individuals with no LoFs: 124734
Homozygous LoFs: 1
Heterozygous LoFs: 61
Defined: 124796
p: 0.000248

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.33	694	889	0.780	0.0000461	11082
Missense (PolyPhen)		138	285.05	0.48413		3443
Synonymous	-0.520	320	308	1.04	0.0000156	3138
Loss of Function	6.21	29	93.9	0.309	0.00000559	1076

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00039	0.00039	rare
Latino/Admixed American	0.00041	0.00038	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00027	0.00026	rare
South Asian	0.00034	0.00033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: E3 ubiquitin-protein ligase involved in DNA repair. Upon genotoxic stress, accepts ubiquitin from the UBE2N-UBE2V2 E2 complex and transfers it to 'Lys-164' of PCNA which had been monoubiquitinated by UBE2A/B-RAD18, promoting the formation of non-canonical poly-ubiquitin chains linked through 'Lys-63'. {ECO:0000269|PubMed:17108083, ECO:0000269|PubMed:17130289, ECO:0000269|PubMed:18719106}.;

Recessive Scores

pRec: 0.106

Intolerance Scores

LoFtool: 0.266
RVIS EVS: -1.06
RVIS percentile EVS: 7.58

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.751

Gene Damage Prediction

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