ADPRHL1

Summary

ADPRHL1 (ADP-ribosylhydrolase like 1, HGNC:21303) is a protein-coding gene on chromosome 13q34, encoding Inactive ADP-ribosyltransferase ARH2 (Q8NDY3). Required for myofibril assembly and outgrowth of the cardiac chambers in the developing heart.

ADP-ribosylation is a reversible posttranslational modification used to regulate protein function. ADP-ribosyltransferases (see ART1; MIM 601625) transfer ADP-ribose from NAD+ to the target protein, and ADP-ribosylhydrolases, such as ADPRHL1, reverse the reaction (Glowacki et al., 2002 [PubMed 12070318]).

Source: NCBI Gene 113622 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 128 total — 13 pathogenic, 2 likely-pathogenic
• MANE Select transcript: NM_001394807

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21303
Approved symbol	ADPRHL1
Name	ADP-ribosylhydrolase like 1
Location	13q34
Locus type	gene with protein product
Status	Approved
Aliases	ARH2
Ensembl gene	ENSG00000153531
Ensembl biotype	protein_coding
OMIM	610620
Entrez	113622

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000356501, ENST00000375418, ENST00000413169, ENST00000612156, ENST00000682618

RefSeq mRNA: 5 — MANE Select: NM_001394807 NM_001304433, NM_001375393, NM_001394807, NM_138430, NM_199162

CCDS: CCDS91840, CCDS91841, CCDS9535, CCDS9536

Canonical transcript exons

ENST00000612156 — 8 exons

Exon	Start	End
ENSE00001011292	113424217	113424349
ENSE00001011293	113428952	113429092
ENSE00001097325	113433742	113433867
ENSE00001467035	113453224	113453488
ENSE00003650806	113444425	113444589
ENSE00003743299	113399611	113408220
ENSE00003787740	113425052	113425179
ENSE00003791159	113422826	113422979

Expression profiles

Bgee: expression breadth ubiquitous, 222 present calls, max score 99.42.

FANTOM5 (CAGE): breadth broad, TPM avg 1.8169 / max 157.5580, expressed in 379 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
138350	0.6573	52
138349	0.5954	228
207119	0.3004	150
138352	0.1696	53
138353	0.0564	20
138351	0.0212	15
138354	0.0090	3
138355	0.0076	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ventricle myocardium	UBERON:0006566	99.42	gold quality
cardiac muscle of right atrium	UBERON:0003379	99.26	gold quality
apex of heart	UBERON:0002098	99.06	gold quality
right atrium auricular region	UBERON:0006631	98.23	gold quality
cardiac atrium	UBERON:0002081	98.11	gold quality
heart left ventricle	UBERON:0002084	98.10	gold quality
gastrocnemius	UBERON:0001388	98.08	gold quality
cardiac ventricle	UBERON:0002082	98.02	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.90	gold quality
myocardium	UBERON:0002349	97.17	gold quality
muscle of leg	UBERON:0001383	96.84	gold quality
heart right ventricle	UBERON:0002080	95.94	gold quality
tibialis anterior	UBERON:0001385	95.45	silver quality
heart	UBERON:0000948	95.13	gold quality
skeletal muscle tissue	UBERON:0001134	94.51	gold quality
quadriceps femoris	UBERON:0001377	94.24	gold quality
vastus lateralis	UBERON:0001379	94.06	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	93.90	gold quality
biceps brachii	UBERON:0001507	92.36	gold quality
muscle tissue	UBERON:0002385	92.31	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	92.17	gold quality
deltoid	UBERON:0001476	90.33	gold quality
tibia	UBERON:0000979	89.32	gold quality
body of tongue	UBERON:0011876	85.53	gold quality
ileal mucosa	UBERON:0000331	81.77	silver quality
tongue	UBERON:0001723	81.75	gold quality
trigeminal ganglion	UBERON:0001675	81.69	gold quality
vena cava	UBERON:0004087	79.96	gold quality
pericardium	UBERON:0002407	78.96	gold quality
trachea	UBERON:0003126	78.41	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.77

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

43 targeting ADPRHL1, 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-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-4716-3P	99.69	66.73	1022
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-7155-3P	99.57	66.48	794
HSA-MIR-3616-5P	99.55	67.02	989
HSA-MIR-573	99.55	67.44	955
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-6733-3P	99.54	67.80	1281
HSA-MIR-653-5P	99.46	67.35	1300
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-1286	99.09	66.23	1046
HSA-MIR-328-5P	99.08	64.65	1000
HSA-MIR-8070	99.07	69.30	1303
HSA-MIR-140-3P	99.04	67.69	1324
HSA-MIR-625-5P	99.02	68.64	2031
HSA-MIR-1909-5P	98.94	64.01	484

Literature-anchored findings (GeneRIF, showing 3)

• Hybrid human-Xenopus Adprhl1 protein constructs were produced by utilizing restriction sites from one species and engineering the same site into the second species by PCR. Hearts containing human ADPRHL1 developed normally. Engineered human-Xenopus hybrid proteins cause extensive branching of myofibrils with sarcomere division occurring at the actin-Z-disc boundary. (PMID:27217161)
• Non-genetic and genetic rewiring underlie adaptation to hypomorphic alleles of an essential gene. (PMID:34528284)
• The pseudoenzyme ADPRHL1 affects cardiac function by regulating the ROCK pathway. (PMID:37880701)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	adprhl1	ENSDARG00000041589
mus_musculus	Adprhl1	ENSMUSG00000031448
rattus_norvegicus		ENSRNOG00000071336

Paralogs (1): ADPRH (ENSG00000144843)

Protein

Protein identifiers

Inactive ADP-ribosyltransferase ARH2 — Q8NDY3 (reviewed: Q8NDY3)

Alternative names: ADP-ribosylhydrolase-like protein 1, [Protein ADP-ribosylarginine] hydrolase-like protein 1

All UniProt accessions (4): Q8NDY3, A0A0U1RQK4, A0A804HI13, X6RL45

UniProt curated annotations — full annotation on UniProt →

Function. Required for myofibril assembly and outgrowth of the cardiac chambers in the developing heart. Appears to be catalytically inactive, showing no activity against O-acetyl-ADP-ribose.

Subcellular location. Cytoplasm. Myofibril. Sarcomere.

Similarity. Belongs to the ADP-ribosylglycohydrolase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8NDY3-1	1	yes
Q8NDY3-2	2

RefSeq proteins (5): NP_001291362, NP_001362322, NP_001381736, NP_612439, NP_954631 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005502	Ribosyl_crysJ1	Family
IPR012108	ADP-ribosylarg_hydro	Family
IPR036705	Ribosyl_crysJ1_sf	Homologous_superfamily
IPR050792	ADP-ribosylglycohydrolase	Family

Pfam: PF03747

UniProt features (4 total): chain 1, modified residue 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NDY3-F1	93.80	0.85

Functional residue map

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

Post-translational modifications (1): 27

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 115 (showing top): GOBP_CARDIAC_CHAMBER_DEVELOPMENT, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_CARDIAC_CHAMBER_MORPHOGENESIS, GOBP_GROWTH, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_CARDIAC_MYOFIBRIL_ASSEMBLY, EVI1_05, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_CELLULAR_COMPONENT_ASSEMBLY_INVOLVED_IN_MORPHOGENESIS, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, GOBP_HEART_MORPHOGENESIS, chr13q34, GOBP_CARDIAC_MUSCLE_CELL_DIFFERENTIATION, GOBP_ACTOMYOSIN_STRUCTURE_ORGANIZATION, GOBP_ORGAN_GROWTH

GO Biological Process (3): cardiac chamber ballooning (GO:0003242), protein de-ADP-ribosylation (GO:0051725), cardiac myofibril assembly (GO:0055003)

GO Molecular Function (4): magnesium ion binding (GO:0000287), ADP-ribosylarginine-[protein] hydrolase activity (GO:0003875), hydrolase activity, hydrolyzing N-glycosyl compounds (GO:0016799), metal ion binding (GO:0046872)

GO Cellular Component (2): sarcomere (GO:0030017), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cardiac chamber morphogenesis	1
growth involved in heart morphogenesis	1
protein modification process	1
myofibril assembly	1
cardiac muscle cell development	1
metal ion binding	1
hydrolase activity, hydrolyzing N-glycosyl compounds	1
catalytic activity, acting on a protein	1
hydrolase activity, acting on glycosyl bonds	1
cation binding	1
myofibril	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

670 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADPRHL1	GRTP1	Q5TC63	542
ADPRHL1	SLC9D1	Q6UWJ1	532
ADPRHL1	ABTB1	Q969K4	491
ADPRHL1	LSMEM2	Q8N112	485
ADPRHL1	ZNF541	Q9H0D2	437
ADPRHL1	DCUN1D2	Q6PH85	430
ADPRHL1	GALR1	P47211	377
ADPRHL1	DPY19L3	Q6ZPD9	376
ADPRHL1	MANEAL	Q5VSG8	371
ADPRHL1	CCDC61	Q9Y6R9	371
ADPRHL1	ATP4B	P51164	360
ADPRHL1	GOLGA6L6	A8MZA4	359
ADPRHL1	ACYP1	P07311	358
ADPRHL1	BRICD5	Q6PL45	356
ADPRHL1	PCID2	Q5JVF3	355

IntAct

0 interactions, top by confidence:

BioGRID (3): ADPRHL1 (Reconstituted Complex), ADPRHL1 (Affinity Capture-MS), ADPRHL1 (Affinity Capture-MS)

ESM2 similar proteins: B1PK17, B4G0F3, B8BKI7, C6JS30, H3BCW1, O00116, P31254, P31754, P52624, P54922, P54923, P97275, Q01415, Q02589, Q0ZHH6, Q16798, Q16831, Q28FQ6, Q32KR8, Q3SYV9, Q3ZBM1, Q5R6J8, Q5RCJ0, Q5XIB3, Q5XIG6, Q5XJB9, Q5ZI51, Q66HT8, Q68FH4, Q6AZR2, Q6DD88, Q84VX0, Q8BGK2, Q8BGT5, Q8BMF3, Q8C0I1, Q8CG72, Q8NDY3, Q8TD30, Q91WS4

Diamond homologs: P54922, P54923, Q02589, Q32KR8, Q3ZBM1, Q54H71, Q5RCJ0, Q5XIB3, Q5XJB9, Q6AZR2, Q8BGK2, Q8NDY3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	13
Likely pathogenic	2
Uncertain significance	85
Likely benign	18
Benign	3

Top pathogenic / likely-pathogenic (15)

Variant ID	HGVS	Classification
148895	GRCh38/hg38 13q34(chr13:111355741-114340331)x1	Pathogenic
152704	GRCh38/hg38 13q34(chr13:111200986-114340331)x1	Pathogenic
1703542	GRCh37/hg19 13q34(chr13:110428062-115107733)	Pathogenic
3024583	GRCh37/hg19 13q34(chr13:113158346-115091756)x1	Pathogenic
3391921	GRCh37/hg19 13q34(chr13:112014531-115107733)x1	Pathogenic
394630	GRCh37/hg19 13q34(chr13:112091743-115092510)x1	Pathogenic
441710	GRCh37/hg19 13q33.3-34(chr13:109151651-115107733)x1	Pathogenic
564069	GRCh37/hg19 13q34(chr13:112530842-115107733)x1	Pathogenic
564074	GRCh37/hg19 13q33.3-34(chr13:109771548-115107733)x1	Pathogenic
57714	GRCh38/hg38 13q34(chr13:111541166-113671678)x1	Pathogenic
59927	GRCh38/hg38 13q34(chr13:111439396-114327173)x3	Pathogenic
59929	GRCh38/hg38 13q34(chr13:112292922-113636272)x3	Pathogenic
686178	GRCh37/hg19 13q34(chr13:111568865-115107733)x1	Pathogenic
1340720	GRCh37/hg19 13q34(chr13:113626234-115107733)x3	Likely pathogenic
979996	GRCh37/hg19 13q34(chr13:112069981-115107733)x3	Likely pathogenic

SpliceAI

1398 predictions. Top by Δscore:

Variant	Effect	Δscore
13:113422975:CTCCC:C	acceptor_gain	1.0000
13:113422976:TCCC:T	acceptor_gain	1.0000
13:113422977:CCC:C	acceptor_gain	1.0000
13:113422977:CCCC:C	acceptor_gain	1.0000
13:113422978:CCC:C	acceptor_gain	1.0000
13:113422979:CCT:C	acceptor_loss	1.0000
13:113422980:C:CC	acceptor_gain	1.0000
13:113422980:CTGA:C	acceptor_loss	1.0000
13:113422981:T:G	acceptor_loss	1.0000
13:113433739:TA:T	donor_loss	1.0000
13:113433740:A:AC	donor_gain	1.0000
13:113433740:AC:A	donor_gain	1.0000
13:113433740:ACCTG:A	donor_loss	1.0000
13:113433741:C:CC	donor_gain	1.0000
13:113433741:C:CG	donor_loss	1.0000
13:113433741:CC:C	donor_gain	1.0000
13:113433741:CCT:C	donor_gain	1.0000
13:113433741:CCTG:C	donor_gain	1.0000
13:113433741:CCTGT:C	donor_gain	1.0000
13:113433863:TGAGC:T	acceptor_gain	1.0000
13:113433864:GAGC:G	acceptor_gain	1.0000
13:113433864:GAGCC:G	acceptor_gain	1.0000
13:113433865:AGC:A	acceptor_gain	1.0000
13:113433866:GC:G	acceptor_gain	1.0000
13:113433866:GCC:G	acceptor_loss	1.0000
13:113433866:GCCT:G	acceptor_gain	1.0000
13:113433867:CC:C	acceptor_gain	1.0000
13:113433867:CCTGT:C	acceptor_gain	1.0000
13:113433868:C:CC	acceptor_gain	1.0000
13:113433869:T:A	acceptor_loss	1.0000

AlphaMissense

12739 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:113425144:A:G	W228R	0.999
13:113425144:A:T	W228R	0.999
13:113433765:C:G	R161P	0.998
13:113433779:G:C	S156R	0.998
13:113433779:G:T	S156R	0.998
13:113433781:T:G	S156R	0.998
13:113429024:A:G	W192R	0.996
13:113429024:A:T	W192R	0.996
13:113424337:A:G	W263R	0.995
13:113424337:A:T	W263R	0.995
13:113429084:C:G	G172R	0.995
13:113429092:C:T	G169D	0.995
13:113433828:C:T	G140D	0.995
13:113444449:A:G	W119R	0.995
13:113444449:A:T	W119R	0.995
13:113429083:C:T	G172D	0.994
13:113429088:G:C	F170L	0.994
13:113429088:G:T	F170L	0.994
13:113429090:A:G	F170L	0.994
13:113453242:C:G	A66P	0.994
13:113429068:G:T	A177D	0.993
13:113433768:C:T	G160D	0.993
13:113433829:C:G	G140R	0.993
13:113424253:A:G	W291R	0.992
13:113424253:A:T	W291R	0.992
13:113424285:G:T	A280D	0.992
13:113425121:C:A	R235S	0.992
13:113425121:C:G	R235S	0.992
13:113425142:C:A	W228C	0.992
13:113425142:C:G	W228C	0.992

dbSNP variants (sampled 300 via entrez): RS1000043345 (13:113437957 A>C,G), RS1000124456 (13:113451861 G>A,T), RS1000130924 (13:113448115 C>T), RS1000153044 (13:113401934 C>T), RS1000155587 (13:113451664 C>T), RS1000217099 (13:113418032 A>G), RS1000220398 (13:113402932 G>A), RS1000227895 (13:113406484 A>C,G), RS1000234293 (13:113413482 C>T), RS1000259065 (13:113406701 G>A), RS1000512422 (13:113410361 C>T), RS1000572977 (13:113443349 C>T), RS1000583084 (13:113405464 G>A,T), RS1000629347 (13:113413754 G>A), RS1000636618 (13:113438701 T>A,C)

Disease associations

OMIM: gene MIM:610620 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST010321_148	PR interval	4.000000e-19
GCST012099_10	Hypertrophic cardiomyopathy (sarcomere negative)	4.000000e-09
GCST012489_147	Heel bone mineral density x serum urate levels interaction	3.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004462	PR interval
EFO:0004531	urate measurement
EFO:0009270	heel bone mineral density

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
arsenite	affects binding, increases reaction	1
zinc chromate	increases abundance, increases expression	1
chromium hexavalent ion	increases abundance, increases expression	1
bisphenol S	increases methylation	1
jinfukang	affects cotreatment, increases expression	1
2,3,5-trichloro-6-phenyl-(1,4)benzoquinone	increases expression	1
Temozolomide	decreases expression	1
Sunitinib	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	increases expression, affects cotreatment	1
Doxorubicin	decreases expression	1
Estradiol	decreases expression	1
Ozone	affects expression, increases abundance	1
Smoke	affects expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	affects expression	1
Toluene	decreases expression, increases methylation	1
Triclosan	decreases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	increases methylation	1
Okadaic Acid	increases expression	1
Acrylamide	increases expression	1

Clinical trials (associated diseases)

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