SHPRH

Summary

SHPRH (SNF2 histone linker PHD RING helicase, HGNC:19336) is a protein-coding gene on chromosome 6q24.3, encoding E3 ubiquitin-protein ligase SHPRH (Q149N8). E3 ubiquitin-protein ligase involved in DNA repair.

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]).

Source: NCBI Gene 257218 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 202 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001042683

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19336
Approved symbol	SHPRH
Name	SNF2 histone linker PHD RING helicase
Location	6q24.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ90837, KIAA2023, bA545I5.2
Ensembl gene	ENSG00000146414
Ensembl biotype	protein_coding
OMIM	608048
Entrez	257218

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 6 protein_coding, 3 nonsense_mediated_decay, 2 retained_intron

ENST00000275233, ENST00000367505, ENST00000417762, ENST00000433355, ENST00000438092, ENST00000519632, ENST00000520752, ENST00000521977, ENST00000523276, ENST00000629427, ENST00000915805

RefSeq mRNA: 4 — MANE Select: NM_001042683 NM_001042683, NM_001370327, NM_001370328, NM_173082

CCDS: CCDS43513, CCDS47496

Canonical transcript exons

ENST00000275233 — 30 exons

Exon	Start	End
ENSE00000975748	145893215	145893393
ENSE00000975749	145888020	145888100
ENSE00001084887	145945381	145945637
ENSE00001084897	145952349	145952478
ENSE00001084901	145954690	145955354
ENSE00001444796	145884807	145886787
ENSE00002433802	145894150	145894236
ENSE00002475402	145910448	145910636
ENSE00002526843	145894885	145894977
ENSE00003459188	145927189	145927277
ENSE00003461676	145922663	145922836
ENSE00003473335	145948272	145948350
ENSE00003485993	145921167	145921392
ENSE00003486353	145922286	145922348
ENSE00003516016	145950264	145950482
ENSE00003518815	145923643	145923785
ENSE00003536441	145918131	145918232
ENSE00003543262	145943143	145943802
ENSE00003557842	145940723	145940801
ENSE00003562066	145933057	145933178
ENSE00003582037	145941623	145941874
ENSE00003601677	145913478	145913549
ENSE00003617032	145934907	145935163
ENSE00003625146	145935278	145935441
ENSE00003632897	145926204	145926296
ENSE00003640201	145924739	145924846
ENSE00003684924	145947493	145947643
ENSE00003689439	145946233	145946341
ENSE00003692039	145919348	145919491
ENSE00003842738	145963731	145964358

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 92.20.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.3767 / max 168.9697, expressed in 1733 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
76079	9.5085	1705
76076	0.9679	518
76080	0.8461	466
76081	0.0543	16

Top tissues by expression

260 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	92.20	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.37	gold quality
adrenal tissue	UBERON:0018303	90.27	gold quality
epithelial cell of pancreas	CL:0000083	89.15	gold quality
sural nerve	UBERON:0015488	86.88	gold quality
pigmented layer of retina	UBERON:0001782	84.56	gold quality
retina	UBERON:0000966	84.53	gold quality
germinal epithelium of ovary	UBERON:0001304	84.42	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.09	gold quality
tibia	UBERON:0000979	83.63	gold quality
upper leg skin	UBERON:0004262	83.24	gold quality
bone marrow cell	CL:0002092	82.94	gold quality
left ovary	UBERON:0002119	82.89	gold quality
upper arm skin	UBERON:0004263	82.55	gold quality
ovary	UBERON:0000992	82.44	gold quality
skin of hip	UBERON:0001554	82.09	gold quality
mucosa of paranasal sinus	UBERON:0005030	81.83	gold quality
seminal vesicle	UBERON:0000998	81.64	gold quality
right ovary	UBERON:0002118	81.39	gold quality
parietal pleura	UBERON:0002400	81.21	gold quality
colonic epithelium	UBERON:0000397	81.11	gold quality
ventricular zone	UBERON:0003053	80.88	gold quality
jejunal mucosa	UBERON:0000399	80.72	gold quality
tonsil	UBERON:0002372	80.67	gold quality
ileal mucosa	UBERON:0000331	80.42	gold quality
corpus callosum	UBERON:0002336	80.42	gold quality
eye	UBERON:0000970	80.37	gold quality
right hemisphere of cerebellum	UBERON:0014890	79.99	gold quality
body of uterus	UBERON:0009853	79.95	gold quality
uterine cervix	UBERON:0000002	79.61	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

111 targeting SHPRH, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-374A-5P	99.90	71.34	2923

Literature-anchored findings (GeneRIF, showing 14)

• SHPRH maps to 6q24 and is a possible candidate for the tumor suppressor gene reported from that region. (PMID:12837266)
• SHPRH function is an important deterrent to mutagenesis and carcinogenesis in humans (PMID:17108083)
• We report that a putative tumor suppressor gene, SHPRH, is a human orthologue of yeast RAD5.The yRad5/SHPRH-dependent pathway is a conserved and fundamental DNA repair mechanism that protects the genome from genotoxic stress. (PMID:17130289)
• HLTF and SHPRH are functional homologues of yeast Rad5 that cooperatively mediate PCNA polyubiquitination and maintain genomic stability. (PMID:18719106)
• HLTF and SHPRH suppress mutagenesis in a damage-specific manner, preventing mutations induced by UV rays and methyl methanesulfonate. (PMID:21396873)
• evidence that SHPRH functions in rRNA transcription through its interaction with histone H3 in a mammalian target of rapamycin (mTOR)-dependent manner (PMID:28400511)
• This study suggests that SHPRH could be a link between mTOR-mediated epigenetic regulations and rRNA transcription, while concomitantly affecting genomic integrity. (PMID:29139335)
• A novel perspective regarding circRNA function in physiological and pathological processes: specifically, SHPRH-146aa generated from overlapping genetic codes of circ-SHPRH is a tumor suppressor in human glioblastoma. (PMID:29343848)
• circ-0001649 regulated behaviors of hepatocellular carcinoma cells by targeting SHPRH; circ-0001649 served as a ceRNA to sponge miR-127-5p, miR-612 and miR-4688, thus activating SHPRH (PMID:31137016)
• Helicase-Like Transcription Factor HLTF and E3 Ubiquitin Ligase SHPRH Confer DNA Damage Tolerance through Direct Interactions with Proliferating Cell Nuclear Antigen (PCNA). (PMID:31973093)
• The Human RAD5 Homologs, HLTF and SHPRH, Have Separate Functions in DNA Damage Tolerance Dependent on The DNA Lesion Type. (PMID:32192191)
• KMT2B promotes SHPRH expression to regulate (131)I sensitivity in thyroid carcinoma cells by affecting FYN protein stability. (PMID:34606908)
• A peptide encoded by the circular form of the SHPRH gene induces apoptosis in neuroblastoma cells. (PMID:38282862)
• Integrative genomics identifies SHPRH as a tumor suppressor gene in lung adenocarcinoma that regulates DNA damage response. (PMID:38890444)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	shprh	ENSDARG00000075884
mus_musculus	Shprh	ENSMUSG00000090112
rattus_norvegicus	Shprh	ENSRNOG00000014450
caenorhabditis_elegans		WBGENE00020235

Paralogs (30): HLTF (ENSG00000071794), SMARCA2 (ENSG00000080503), SRCAP (ENSG00000080603), ATRX (ENSG00000085224), RAD54L (ENSG00000085999), BTAF1 (ENSG00000095564), CHD8 (ENSG00000100888), SMARCA1 (ENSG00000102038), CHD4 (ENSG00000111642), CHD5 (ENSG00000116254), TTF2 (ENSG00000116830), HELLS (ENSG00000119969), ZRANB3 (ENSG00000121988), CHD6 (ENSG00000124177), SMARCA4 (ENSG00000127616), INO80 (ENSG00000128908), CHD1L (ENSG00000131778), SMARCAL1 (ENSG00000138375), SMARCA5 (ENSG00000153147), CHD1 (ENSG00000153922), SMARCAD1 (ENSG00000163104), RAD54L2 (ENSG00000164080), CHD3 (ENSG00000170004), CHD7 (ENSG00000171316), CHD2 (ENSG00000173575), CHD9 (ENSG00000177200), EP400 (ENSG00000183495), ERCC6L (ENSG00000186871), RAD54B (ENSG00000197275), ERCC6 (ENSG00000225830)

Protein

Protein identifiers

E3 ubiquitin-protein ligase SHPRH — Q149N8 (reviewed: Q149N8)

Alternative names: RING-type E3 ubiquitin transferase SHPRH, SNF2, histone-linker, PHD and RING finger domain-containing helicase

All UniProt accessions (5): Q149N8, A0A0D9SFM0, H0YBI0, H7C2W2, Q5JT88

UniProt curated annotations — full annotation on UniProt →

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’.

Subunit / interactions. Homodimer. Interacts with HLTF, PCNA, UBE2N and RAD18.

Tissue specificity. Broadly expressed.

Domain organisation. The RING finger mediates E3 ubiquitin ligase activity.

Pathway. Protein modification; protein ubiquitination.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the SNF2/RAD54 helicase family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q149N8-1	1	yes
Q149N8-2	2
Q149N8-4	3
Q149N8-5	4

RefSeq proteins (4): NP_001036148, NP_001357256, NP_001357257, NP_775105 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000330	SNF2_N	Domain
IPR001650	Helicase_C-like	Domain
IPR001841	Znf_RING	Domain
IPR001965	Znf_PHD	Domain
IPR005818	Histone_H1/H5_H15	Domain
IPR011011	Znf_FYVE_PHD	Homologous_superfamily
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR014001	Helicase_ATP-bd	Domain
IPR017907	Znf_RING_CS	Conserved_site
IPR019786	Zinc_finger_PHD-type_CS	Conserved_site
IPR027370	Znf-RING_euk	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR038718	SNF2-like_sf	Homologous_superfamily
IPR048686	SHPRH_helical_1st	Domain
IPR048695	SHPRH_helical_2nd	Domain
IPR049730	SNF2/RAD54-like_C	Domain
IPR052583	SHPRH-like	Family

Pfam: PF00176, PF00271, PF00538, PF13445, PF21324, PF21325

UniProt features (63 total): helix 16, splice variant 9, sequence variant 6, turn 6, sequence conflict 5, domain 4, strand 4, compositionally biased region 3, modified residue 2, zinc finger region 2, region of interest 2, chain 1, binding site 1, mutagenesis site 1, short sequence motif 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
4QN1	X-RAY DIFFRACTION	2.48
2M85	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q149N8-F1	71.04	0.20

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (1): 373–380

Post-translational modifications (2): 266, 635

Mutagenesis-validated functional residues (1):

Position	Phenotype
1432	abolishes e3 activity.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-8866654	E3 ubiquitin ligases ubiquitinate target proteins
R-HSA-392499	Metabolism of proteins
R-HSA-597592	Post-translational protein modification
R-HSA-8852135	Protein ubiquitination

MSigDB gene sets: 147 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, TGCGCANK_UNKNOWN, GOBP_DNA_DAMAGE_RESPONSE, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_PROTEIN_POLYUBIQUITINATION, GOBP_PROTEIN_DNA_COMPLEX_ORGANIZATION, GOBP_CHROMATIN_REMODELING, CHANDRAN_METASTASIS_UP, GOCC_PROTEIN_DNA_COMPLEX, SANSOM_APC_TARGETS_REQUIRE_MYC, GOBP_DNA_METABOLIC_PROCESS, GOBP_DNA_REPAIR, AGGTGCA_MIR500, GOMF_ACYLTRANSFERASE_ACTIVITY, GOMF_AMINOACYLTRANSFERASE_ACTIVITY

GO Biological Process (5): protein polyubiquitination (GO:0000209), DNA repair (GO:0006281), nucleosome assembly (GO:0006334), DNA damage response (GO:0006974), protein ubiquitination (GO:0016567)

GO Molecular Function (12): DNA binding (GO:0003677), helicase activity (GO:0004386), ubiquitin-protein transferase activity (GO:0004842), ATP binding (GO:0005524), zinc ion binding (GO:0008270), hydrolase activity (GO:0016787), ubiquitin protein ligase binding (GO:0031625), ubiquitin protein ligase activity (GO:0061630), nucleotide binding (GO:0000166), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (3): nucleosome (GO:0000786), nucleoplasm (GO:0005654), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Protein ubiquitination	1
Metabolism of proteins	1
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
catalytic activity	2
protein ubiquitination	1
DNA metabolic process	1
DNA damage response	1
chromatin organization	1
nucleosome organization	1
protein-DNA complex assembly	1
cellular response to stress	1
protein modification by small protein conjugation	1
nucleic acid binding	1
nucleic acid conformation isomerase activity	1
catalytic activity, acting on a nucleic acid	1
ATP-dependent activity	1
ubiquitin-like protein transferase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
transition metal ion binding	1
ubiquitin-like protein ligase binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
cation binding	1
chromatin	1
protein-DNA complex	1
nuclear lumen	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

3051 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SHPRH	RAD18	Q9NS91	969
SHPRH	UBE2V2	Q15819	965
SHPRH	UBE2N	P61088	941
SHPRH	SMARCA2	P51531	739
SHPRH	ZNF609	O15014	732
SHPRH	RAD52	P43351	731
SHPRH	SMARCA4	P51532	691
SHPRH	FOXN2	P32314	667
SHPRH	FBXO30	Q8TB52	616
SHPRH	HFM1	A2PYH4	597
SHPRH	USP1	O94782	578
SHPRH	FANCM	Q8IYD8	570
SHPRH	FBXW7	Q969H0	546
SHPRH	EIF4A3	P38919	531
SHPRH	USP28	Q96RU2	528

IntAct

41 interactions, top by confidence:

A	B	Type	Score
RBBP7	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
RBBP4	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
RBBP7	HAT1	psi-mi:“MI:0914”(association)	0.730
TEPSIN	AP4M1	psi-mi:“MI:0914”(association)	0.700
SHPRH	EDARADD	psi-mi:“MI:0915”(physical association)	0.560
SHPRH	BORCS6	psi-mi:“MI:0915”(physical association)	0.560
EDARADD	SHPRH	psi-mi:“MI:0915”(physical association)	0.560
BORCS6	SHPRH	psi-mi:“MI:0915”(physical association)	0.560
N	NOP56	psi-mi:“MI:0914”(association)	0.530
N	RBM47	psi-mi:“MI:0914”(association)	0.530
RBBP4	TNRC18	psi-mi:“MI:0914”(association)	0.530
RBBP7	SMARCA5	psi-mi:“MI:0914”(association)	0.530
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
SHPRH	HSPA9	psi-mi:“MI:0915”(physical association)	0.400
SHPRH	PPIB	psi-mi:“MI:0915”(physical association)	0.400
USP36	STK25	psi-mi:“MI:0914”(association)	0.350
USP49	ANKRD28	psi-mi:“MI:0914”(association)	0.350
N	RBM47	psi-mi:“MI:0914”(association)	0.350
FKBP5	IFT56	psi-mi:“MI:0914”(association)	0.350
H2BC21	SMCHD1	psi-mi:“MI:0914”(association)	0.350
PARP1	KPNA3	psi-mi:“MI:0914”(association)	0.350
RBBP4	KPNA3	psi-mi:“MI:0914”(association)	0.350

BioGRID (130): SHPRH (Two-hybrid), SHPRH (Two-hybrid), SHPRH (Affinity Capture-MS), SHPRH (Proximity Label-MS), SHPRH (Affinity Capture-MS), SHPRH (Affinity Capture-MS), H3.1 (Reconstituted Complex), SHPRH (Reconstituted Complex), SHPRH (Affinity Capture-Western), POLR1A (Affinity Capture-Western), UBTF (Affinity Capture-Western), HIST1H3A (Affinity Capture-Western), SHPRH (Affinity Capture-Western), SHPRH (Co-localization), SHPRH (Affinity Capture-RNA)

ESM2 similar proteins: A1L3L1, A2RT67, A3KPW7, A4IIA7, A8C750, A8C752, D2HNY3, E1BGQ2, E1C3P4, Q08CL8, Q08DZ8, Q0IHB3, Q149N8, Q1RMU2, Q1RMZ1, Q3MJ13, Q3T1H6, Q5F3F2, Q5RED8, Q5VVJ2, Q5ZJ87, Q66J91, Q69Z66, Q6AYF5, Q6DE97, Q6GR37, Q6P1E7, Q6PNC0, Q6YHU6, Q7TPQ3, Q8BKW4, Q8BXK4, Q8IWR0, Q8IYF3, Q8IZE3, Q8K2I9, Q8NA31, Q8NEN0, Q8NFZ0, Q96EW2

Diamond homologs: A2BGR3, A3KMX0, A4PBL4, A4R227, A6QQR4, A6ZU34, A7EQA8, A7TJI3, A7Z019, B6ZLK2, C0H4W3, E1BB03, E7F1C4, E9PZM4, F1Q8K0, F4I2H2, F4IHS2, F4IV99, F4J9M5, F8VPZ5, O12944, O14646, O14647, O60264, P0CO16, P0CO17, P28370, P31380, P32333, P32849, P36607, P38144, P40201, P40352, P41410, P41877, P43610, P51531, P51532, P53115

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
SHPRH	up-regulates	PCNA	ubiquitination
Ub:E2	“up-regulates activity”	SHPRH	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 40 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
NuRD complex assembly	5	28.2×	1e-04
Interaction of NuRD complexes with transcription factors	5	25.4×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
nucleosome assembly	5	19.0×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

202 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	171
Likely benign	8
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

4877 predictions. Top by Δscore:

Variant	Effect	Δscore
6:145893213:A:AC	donor_gain	1.0000
6:145893214:C:CC	donor_gain	1.0000
6:145893391:CTC:C	acceptor_gain	1.0000
6:145893392:TCCTA:T	acceptor_loss	1.0000
6:145893394:C:CC	acceptor_gain	1.0000
6:145893394:CTAA:C	acceptor_loss	1.0000
6:145894145:CATA:C	donor_loss	1.0000
6:145894146:ATACC:A	donor_loss	1.0000
6:145894147:TAC:T	donor_loss	1.0000
6:145894148:A:C	donor_loss	1.0000
6:145894149:C:A	donor_loss	1.0000
6:145894237:C:CC	acceptor_gain	1.0000
6:145910633:CCCA:C	acceptor_gain	1.0000
6:145910634:CCA:C	acceptor_gain	1.0000
6:145910634:CCAC:C	acceptor_gain	1.0000
6:145910635:CA:C	acceptor_gain	1.0000
6:145910635:CAC:C	acceptor_gain	1.0000
6:145910637:C:CC	acceptor_gain	1.0000
6:145911781:T:TC	acceptor_gain	1.0000
6:145913550:C:CC	acceptor_gain	1.0000
6:145913555:C:CT	acceptor_gain	1.0000
6:145913555:C:T	acceptor_gain	1.0000
6:145913556:A:T	acceptor_gain	1.0000
6:145918125:CAATA:C	donor_loss	1.0000
6:145918126:AATAC:A	donor_loss	1.0000
6:145918127:ATAC:A	donor_loss	1.0000
6:145918128:TA:T	donor_loss	1.0000
6:145918129:ACC:A	donor_loss	1.0000
6:145918130:CC:C	donor_loss	1.0000
6:145918229:CTAC:C	acceptor_gain	1.0000

AlphaMissense

11132 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:145893230:C:G	R1620P	1.000
6:145893238:C:A	R1617S	1.000
6:145893238:C:G	R1617S	1.000
6:145893239:C:A	R1617M	1.000
6:145893239:C:G	R1617T	1.000
6:145893249:C:G	A1614P	1.000
6:145893293:A:T	V1599D	1.000
6:145893320:C:T	G1590E	1.000
6:145893321:C:G	G1590R	1.000
6:145893321:C:T	G1590R	1.000
6:145893344:A:G	L1582P	1.000
6:145893347:A:G	L1581P	1.000
6:145894202:A:G	L1548P	1.000
6:145894891:G:C	F1534L	1.000
6:145894891:G:T	F1534L	1.000
6:145894893:A:G	F1534L	1.000
6:145894895:A:T	V1533D	1.000
6:145894960:T:A	K1511N	1.000
6:145894960:T:G	K1511N	1.000
6:145910540:A:G	C1475R	1.000
6:145910597:A:G	C1456R	1.000
6:145910636:A:G	W1443R	1.000
6:145910636:A:T	W1443R	1.000
6:145913501:A:G	C1435R	1.000
6:145913508:G:C	C1432W	1.000
6:145913509:C:T	C1432Y	1.000
6:145913510:A:G	C1432R	1.000
6:145918147:A:G	L1413P	1.000
6:145933155:A:G	L1005P	1.000
6:145933158:A:G	L1004P	1.000

dbSNP variants (sampled 300 via entrez): RS1000022509 (6:145870428 AT>A,ATT), RS1000039181 (6:145914455 G>A), RS1000044856 (6:145925248 A>G), RS1000051679 (6:145932226 G>C,T), RS1000068755 (6:145888460 G>C), RS1000073335 (6:145901412 T>C), RS1000084039 (6:145931998 T>G), RS1000102762 (6:145958682 G>A), RS1000134491 (6:145919056 A>G), RS1000202393 (6:145908161 T>A), RS1000216769 (6:145926401 A>C,G), RS1000252877 (6:145918846 T>C), RS1000263567 (6:145962061 C>T), RS1000288399 (6:145868240 C>G), RS1000302245 (6:145938614 T>C)

Disease associations

OMIM: gene MIM:608048 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4742294 (PROTEIN-PROTEIN INTERACTION), CHEMBL6066854 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

1 potent at pChembl≥5 of 1 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.54	IC50	2860	nM	MOLIBRESIB

PubChem BioAssay actives

1 with measured affinity, of 7 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178765: Inhibition of SHPRH (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	2.8600	uM

CTD chemical–gene interactions

32 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tetrachlorodibenzodioxin	decreases expression	3
bisphenol A	decreases expression, increases methylation, affects cotreatment	2
Hydrogen Peroxide	affects expression, affects cotreatment, increases expression	2
Quercetin	decreases expression, increases phosphorylation	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
sodium arsenite	decreases expression	1
pentanal	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
Resveratrol	affects cotreatment, increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Atrazine	decreases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Dimethyl Sulfoxide	increases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Theophylline	affects cotreatment, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases expression	1
Vanadates	decreases expression	1
1-Methyl-3-isobutylxanthine	decreases expression, affects cotreatment	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4713761	Binding	Protac activity at CRBN/SHPRH in human BxPC-3 cells assessed as SHPRH degradation incubated for 16 hrs by proteomic analysis	Discovery of a Napabucasin PROTAC as an Effective Degrader of the E3 Ligase ZFP91. — J Med Chem

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B5KX	HAP1 SHPRH (-) 2	Cancer cell line	Male
CVCL_B5KY	HAP1 SHPRH (-) 3	Cancer cell line	Male
CVCL_DX46	HAP1 HLTF (-) SHPRH (-) 1	Cancer cell line	Male
CVCL_DX47	HAP1 HLTF (-) SHPRH (-) 2	Cancer cell line	Male
CVCL_XS79	HAP1 SHPRH (-) 1	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.