CRPPA

Summary

CRPPA (CDP-L-ribitol pyrophosphorylase A, HGNC:37276) is a protein-coding gene on chromosome 7p21.2, encoding D-ribitol-5-phosphate cytidylyltransferase (A4D126). Cytidylyltransferase required for protein O-linked mannosylation.

This gene encodes a 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase-like protein. Mutations in this gene are the cause of Walker-Warburg syndrome. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 729920 — RefSeq curated summary.

At a glance

• Gene–disease (curated): myopathy caused by variation in CRPPA (Definitive, ClinGen) — +4 more curated relationships
• GWAS associations: 9
• Clinical variants (ClinVar): 695 total — 60 pathogenic, 16 likely-pathogenic
• Phenotypes (HPO): 128
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_001101426

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:37276
Approved symbol	CRPPA
Name	CDP-L-ribitol pyrophosphorylase A
Location	7p21.2
Locus type	gene with protein product
Status	Approved
Aliases	hCG_1745121, IspD, Nip
Ensembl gene	ENSG00000214960
Ensembl biotype	protein_coding
OMIM	614631
Entrez	729920

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000399310, ENST00000407010, ENST00000479493, ENST00000674759, ENST00000675257, ENST00000676325, ENST00000856526, ENST00000953342

RefSeq mRNA: 3 — MANE Select: NM_001101426 NM_001101417, NM_001101426, NM_001368197

Canonical transcript exons

ENST00000407010 — 10 exons

Exon	Start	End
ENSE00001537514	16308523	16308627
ENSE00001537556	16376092	16376241
ENSE00001537560	16406061	16406337
ENSE00001554415	16258390	16258482
ENSE00001556741	16258920	16259012
ENSE00001563904	16216066	16216197
ENSE00003552646	16301421	16301466
ENSE00003671426	16278129	16278226
ENSE00003709346	16087525	16091799
ENSE00003845165	16421066	16421538

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 84.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 2.2743 / max 77.9198, expressed in 1167 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
82886	0.9456	622
82885	0.6449	368
82887	0.3916	134
82884	0.1666	34
82883	0.1256	56

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus callosum	UBERON:0002336	84.43	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.35	gold quality
calcaneal tendon	UBERON:0003701	73.34	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	72.46	gold quality
skeletal muscle tissue	UBERON:0001134	70.46	gold quality
prefrontal cortex	UBERON:0000451	70.39	gold quality
stromal cell of endometrium	CL:0002255	70.34	gold quality
colonic epithelium	UBERON:0000397	69.88	gold quality
muscle tissue	UBERON:0002385	68.98	gold quality
superior frontal gyrus	UBERON:0002661	68.47	gold quality
adrenal tissue	UBERON:0018303	67.93	gold quality
liver	UBERON:0002107	67.00	gold quality
endometrium	UBERON:0001295	66.80	gold quality
ventricular zone	UBERON:0003053	66.76	gold quality
frontal cortex	UBERON:0001870	66.73	gold quality
smooth muscle tissue	UBERON:0001135	66.39	gold quality
primary visual cortex	UBERON:0002436	66.39	gold quality
right atrium auricular region	UBERON:0006631	66.35	gold quality
heart left ventricle	UBERON:0002084	66.00	gold quality
heart	UBERON:0000948	65.98	gold quality
placenta	UBERON:0001987	65.71	gold quality
muscle of leg	UBERON:0001383	65.25	gold quality
islet of Langerhans	UBERON:0000006	65.10	gold quality
cerebral cortex	UBERON:0000956	65.10	gold quality
sural nerve	UBERON:0015488	64.84	gold quality
gastrocnemius	UBERON:0001388	64.81	gold quality
hindlimb stylopod muscle	UBERON:0004252	64.70	gold quality
tonsil	UBERON:0002372	64.60	gold quality
urinary bladder	UBERON:0001255	64.59	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	64.59	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.87

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

135 targeting CRPPA, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 12)

• ISPD loss-of-function mutations disrupt dystroglycan O-mannosylation and cause Walker-Warburg syndrome. (PMID:22522420)
• Mutations in ISPD cause Walker-Warburg syndrome and defective glycosylation of alpha-dystroglycan. (PMID:22522421)
• TMEM5 mutations were frequently associated with gonadal dysgenesis and neural tube defects, and ISPD mutations were frequently associated with brain vascular anomalies. (PMID:23217329)
• study report the involvement of the ISPD gene in milder dystroglycanopathy phenotypes ranging from congenital muscular dystrophy to limb-girdle muscular dystrophy and identified allelic ISPD variants in nine cases belonging to seven families (PMID:23288328)
• we identified a novel homozygous c.161G>C/p.G54A variant in ISPD in patients with limb-girdle muscular dystrophy (PMID:23390185)
• study describes a new homozygous missense mutation c.367G>A (p.Gly123Arg) in the ISPD gene in a family of Pakistani origin with 2 cousins from consanguineous parents affected with a congenital muscular dystrophy (CMD) /early limb-girdle muscular dystrophy intermediate phenotype and CMD respectively (PMID:25444434)
• ISPD gene homozygous deletion as a prenatal manifestation of Walker-Warburg syndrome has been found in 3 female fetuses of one family. (PMID:26087224)
• Reduced levels of GYLTL1B and ISPD mRNA associated with increased patient mortality and are the likely cause of alphaDG hypoglycosylation in ccRCC. (PMID:26220087)
• data suggest that the genetic heterogeneity of Limb Girdle Muscular Dystrophy with and without alpha-DG defects is greater than previously realized. (PMID:26404900)
• ISPD and FKTN are essential for the incorporation of ribitol into alpha-dystroglycan. (PMID:27194101)
• A splice site mutation c.1251G>A of ISPD gene is a common cause of congenital muscular dystrophy in Chinese patients. (PMID:31909476)
• Hsa_circ_0079480 promotes tumor progression in acute myeloid leukemia via miR-654-3p/HDGF axis. (PMID:33290265)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	crppa	ENSDARG00000005034
mus_musculus	Crppa	ENSMUSG00000043153
rattus_norvegicus	Crppa	ENSRNOG00000006199

Protein

Protein identifiers

D-ribitol-5-phosphate cytidylyltransferase — A4D126 (reviewed: A4D126)

Alternative names: 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase-like protein, Isoprenoid synthase domain-containing protein

All UniProt accessions (5): A0A140VJM1, A0A6Q8PF75, A0A6Q8PG39, A0A6Q8PHI3, A4D126

UniProt curated annotations — full annotation on UniProt →

Function. Cytidylyltransferase required for protein O-linked mannosylation. Catalyzes the formation of CDP-ribitol nucleotide sugar from D-ribitol 5-phosphate. CDP-ribitol is a substrate of FKTN during the biosynthesis of the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-beta-3-N-acetylglucosamine-beta-4-(phosphate-6-)mannose), a carbohydrate structure present in alpha-dystroglycan (DAG1), which is required for binding laminin G-like domain-containing extracellular proteins with high affinity. Shows activity toward other pentose phosphate sugars and mediates formation of CDP-ribulose or CDP-ribose using CTP and ribulose-5-phosphate or ribose-5-phosphate, respectively. Not Involved in dolichol production.

Subunit / interactions. Homodimer.

Subcellular location. Cytoplasm. Cytosol.

Tissue specificity. Ubiquitously expressed, with high expression in brain.

Disease relevance. Muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A7 (MDDGA7) [MIM:614643] An autosomal recessive disorder characterized by congenital muscular dystrophy associated with cobblestone lissencephaly and other brain anomalies, eye malformations, profound intellectual disability, and death usually in the first years of life. Included diseases are the more severe Walker-Warburg syndrome and the slightly less severe muscle-eye-brain disease. The disease is caused by variants affecting the gene represented in this entry. Muscular dystrophy-dystroglycanopathy limb-girdle C7 (MDDGC7) [MIM:616052] A form of muscular dystrophy resulting from defective glycosylation of alpha-dystroglycan, and characterized by a limb-girdle phenotype with muscular weakness apparent after ambulation is achieved. MDDGC7 individuals do not show epilepsy, intellectual disability, structural eye/brain abnormalities, or white matter changes. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Protein modification; protein glycosylation.

Similarity. Belongs to the IspD/TarI cytidylyltransferase family. IspD subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
A4D126-1	1	yes
A4D126-2	2

RefSeq proteins (3): NP_001094887, NP_001094896, NP_001355126 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR018294	ISPD_synthase_CS	Conserved_site
IPR029044	Nucleotide-diphossugar_trans	Homologous_superfamily
IPR034683	IspD/TarI	Family
IPR040635	ISPD_C	Domain

Pfam: PF01128, PF18706

Enzyme classification (BRENDA):

• EC 2.7.7.40 — D-ribitol-5-phosphate cytidylyltransferase (BRENDA: 10 organisms, 18 substrates, 2 inhibitors, 12 Km, 6 kcat entries)

Substrate kinetics (BRENDA)

2 substrates with measured Km, best-characterized 2. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
CTP	0.0085–0.39	6
D-RIBITOL 5-PHOSPHATE	0.0147–1.28	6

Catalyzed reactions (Rhea), 3 shown:

• D-ribitol 5-phosphate + CTP + H(+) = CDP-L-ribitol + diphosphate (RHEA:12456)
• D-ribulose 5-phosphate + CTP + H(+) = CDP-D-ribulose + diphosphate (RHEA:53612)
• D-ribose 5-phosphate + CTP + H(+) = CDP-D-ribose + diphosphate (RHEA:53872)

UniProt features (58 total): helix 18, sequence variant 16, strand 16, site 4, chain 1, region of interest 1, turn 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4CVH	X-RAY DIFFRACTION	2.39

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A4D126-F1	88.63	0.74

Functional residue map

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

Catalytic / active sites (4): 59 (transition state stabilizer); 66 (transition state stabilizer); 205 (positions substrate for the nucleophilic attack); 263 (positions substrate for the nucleophilic attack)

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9939291	Matriglycan biosynthesis on DAG1

MSigDB gene sets: 313 (showing top): GOBP_NEUROGENESIS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_LIPID_BIOSYNTHETIC_PROCESS, GOBP_CELL_PROJECTION_ORGANIZATION, GOBP_ISOPRENOID_BIOSYNTHETIC_PROCESS, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, GOBP_PROTEIN_O_LINKED_GLYCOSYLATION, GOBP_ISOPRENOID_METABOLIC_PROCESS, GOBP_GLYCOPROTEIN_METABOLIC_PROCESS, GOMF_PROTEIN_DIMERIZATION_ACTIVITY, GOMF_PROTEIN_HOMODIMERIZATION_ACTIVITY, YOSHIMURA_MAPK8_TARGETS_UP, GOMF_TRANSFERASE_ACTIVITY_TRANSFERRING_PHOSPHORUS_CONTAINING_GROUPS

GO Biological Process (4): axon guidance (GO:0007411), isoprenoid biosynthetic process (GO:0008299), protein O-linked glycosylation via mannose (GO:0035269), obsolete protein glycosylation (GO:0006486)

GO Molecular Function (6): protein homodimerization activity (GO:0042803), D-ribitol-5-phosphate cytidylyltransferase activity (GO:0047349), cytidylyltransferase activity (GO:0070567), catalytic activity (GO:0003824), transferase activity (GO:0016740), nucleotidyltransferase activity (GO:0016779)

GO Cellular Component (2): cytosol (GO:0005829), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
DAG1 glycosylations	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
axonogenesis	1
neuron projection guidance	1
isoprenoid metabolic process	1
lipid biosynthetic process	1
protein O-linked glycosylation	1
identical protein binding	1
protein dimerization activity	1
cytidylyltransferase activity	1
nucleotidyltransferase activity	1
molecular_function	1
catalytic activity	1
transferase activity, transferring phosphorus-containing groups	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1625 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CRPPA	FKTN	O75072	792
CRPPA	FKRP	Q9H9S5	760
CRPPA	POMT1	Q9Y6A1	756
CRPPA	RXYLT1	Q9Y2B1	752
CRPPA	POMT2	Q9UKY4	751
CRPPA	B4GAT1	O43505	746
CRPPA	POMGNT2	Q8NAT1	745
CRPPA	POMK	Q9H5K3	706
CRPPA	DAG1	Q14118	701
CRPPA	POMGNT1	Q8WZA1	695
CRPPA	B3GALNT2	Q8NCR0	681
CRPPA	LARGE1	O95461	670
CRPPA	GMPPB	Q9Y5P6	587
CRPPA	DPM2	O94777	568
CRPPA	DOLK	Q9UPQ8	552

IntAct

3 interactions, top by confidence:

A	B	Type	Score
CRPPA	CCT2	psi-mi:“MI:0915”(physical association)	0.400
M		psi-mi:“MI:0914”(association)	0.350

BioGRID (1): CCT2 (Proximity Label-MS)

ESM2 similar proteins: A0JPF9, A4D126, A4D7T3, A4QNL8, A5PKL6, B2GUS6, C0IN03, E1BCH6, E1BVR9, F1LW30, F1ND48, P19686, P19687, P33402, P48760, P57075, Q02108, Q07DZ7, Q08C84, Q09M05, Q108U1, Q1L5Z9, Q1LZ50, Q28CZ7, Q32PY6, Q3U3W5, Q3UY23, Q4R3W5, Q4ZHS0, Q5REW9, Q5RG49, Q5RJG7, Q5RL51, Q5S6T3, Q5T8I9, Q6GPJ4, Q6NXP6, Q6P2P2, Q7SXA9, Q8BTK5

Diamond homologs: A0A0Q3NN41, A0JPF9, A0LIS2, A1KPR8, A3N0G2, A4D126, A4J0Y3, A4YUQ7, A5D5L4, A5EIY9, A5G938, A5U8Q7, A6U8F8, A6X0N1, A7GJ99, A8ANW1, A8MLB1, A9MF28, A9N2D3, B0B835, B0BCA0, B0BP82, B1I0S9, B1WSY4, B3H1E1, B3PYS4, B3QIL5, B4T457, B4TTW1, B5BEY4, B5F411, B5XV34, B9JW91, B9K8U1, C0PXA7, C1AI41, C4XSW4, E1BCH6, O83525, O84468

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	60
Likely pathogenic	16
Uncertain significance	354
Likely benign	147
Benign	59

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1072533	NC_000007.13:g.(?16445666)(16445982_?)del	Pathogenic
1072534	NC_000007.13:g.(?16131310)(16255832_?)del	Pathogenic
1076250	NM_001101426.4(CRPPA):c.550C>T (p.Arg184Ter)	Pathogenic
1252045	NM_001101426.4(CRPPA):c.790-1G>C	Pathogenic
1342054	NM_001101426.4(CRPPA):c.54_55delinsTGC (p.Ser19fs)	Pathogenic
156454	NM_001101426.4(CRPPA):c.161G>C (p.Gly54Ala)	Pathogenic
1680626	NC_000007.13:g.(?16341026)(16341111_?)del	Pathogenic
1680627	NC_000007.13:g.(?16341026)(16415886_?)del	Pathogenic
1680628	NC_000007.13:g.(?16348128)(16445982_?)del	Pathogenic
1680630	NC_000007.13:g.(?16460671)(16460947_?)del	Pathogenic
1805380	NM_001101426.4(CRPPA):c.258-2A>G	Pathogenic
1983342	NM_001101426.4(CRPPA):c.79_80del (p.Thr27fs)	Pathogenic
2070304	NM_001101426.4(CRPPA):c.17_24dup (p.Ala9fs)	Pathogenic
2078955	NM_001101426.4(CRPPA):c.534+1del	Pathogenic
2122850	NM_001101426.4(CRPPA):c.1092C>A (p.Cys364Ter)	Pathogenic
2142758	NM_001101426.4(CRPPA):c.1137dup (p.Lys380Ter)	Pathogenic
2423709	NC_000007.13:g.(?16415697)(16460947_?)del	Pathogenic
2423710	NC_000007.13:g.(?16297995)(16317871_?)del	Pathogenic
2423714	NC_000007.13:g.(?16131320)(16460947_?)del	Pathogenic
2423715	NC_000007.13:g.(?16131320)(16255842_?)del	Pathogenic
282846	NM_001101426.4(CRPPA):c.643C>T (p.Gln215Ter)	Pathogenic
287129	NM_001101426.4(CRPPA):c.1A>T (p.Met1Leu)	Pathogenic
2924564	NM_001101426.4(CRPPA):c.896del (p.Gly299fs)	Pathogenic
2930168	NM_001101426.4(CRPPA):c.337C>T (p.Gln113Ter)	Pathogenic
2941204	NM_001101426.4(CRPPA):c.6_13dup (p.Pro5fs)	Pathogenic
3062949	GRCh37/hg19 7p21.2(chr7:16313474-16372361)x1	Pathogenic
31561	NM_001101426.4(CRPPA):c.1120-1G>T	Pathogenic
31562	NM_001101426.3(CRPPA):c.(535_684)+6399_(535_684)+14526del	Pathogenic
31563	NM_001101426.4(CRPPA):c.789+2T>G	Pathogenic
31565	NM_001101426.4(CRPPA):c.647C>A (p.Ala216Asp)	Pathogenic

SpliceAI

3332 predictions. Top by Δscore:

Variant	Effect	Δscore
7:16216118:T:TA	donor_gain	1.0000
7:16258388:A:AC	donor_gain	1.0000
7:16258389:C:CT	donor_gain	1.0000
7:16258424:C:CT	donor_gain	1.0000
7:16258425:T:TT	donor_gain	1.0000
7:16278124:CTTA:C	donor_loss	1.0000
7:16278125:TTAC:T	donor_loss	1.0000
7:16278126:TA:T	donor_loss	1.0000
7:16278127:A:AC	donor_gain	1.0000
7:16278128:C:CA	donor_gain	1.0000
7:16278128:CA:C	donor_gain	1.0000
7:16278128:CAT:C	donor_gain	1.0000
7:16278128:CATT:C	donor_gain	1.0000
7:16278128:CATTT:C	donor_gain	1.0000
7:16278223:CTCT:C	acceptor_gain	1.0000
7:16278224:TCT:T	acceptor_gain	1.0000
7:16278224:TCTC:T	acceptor_loss	1.0000
7:16278225:CT:C	acceptor_gain	1.0000
7:16278225:CTC:C	acceptor_gain	1.0000
7:16278226:TCT:T	acceptor_gain	1.0000
7:16278227:C:CC	acceptor_gain	1.0000
7:16278227:CT:C	acceptor_loss	1.0000
7:16278228:T:C	acceptor_loss	1.0000
7:16301419:AC:A	donor_gain	1.0000
7:16301420:CC:C	donor_gain	1.0000
7:16308623:CTACA:C	acceptor_gain	1.0000
7:16406054:GACTT:G	donor_loss	1.0000
7:16406055:ACTT:A	donor_loss	1.0000
7:16406056:CTT:C	donor_loss	1.0000
7:16406057:TTA:T	donor_loss	1.0000

AlphaMissense

2945 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:16376125:A:C	F217L	0.996
7:16376125:A:T	F217L	0.996
7:16376127:A:G	F217L	0.996
7:16376135:G:T	P214H	0.996
7:16376143:A:C	S211R	0.996
7:16376143:A:T	S211R	0.996
7:16376145:T:G	S211R	0.996
7:16308523:C:A	K263N	0.994
7:16308523:C:G	K263N	0.994
7:16406074:G:T	A174D	0.994
7:16406119:C:G	R159T	0.994
7:16406128:T:A	D156V	0.994
7:16421125:C:A	K66N	0.994
7:16421125:C:G	K66N	0.994
7:16308592:A:C	C240W	0.993
7:16308594:A:G	C240R	0.993
7:16376130:C:G	A216P	0.993
7:16376135:G:C	P214R	0.993
7:16406125:G:T	A157D	0.993
7:16406128:T:G	D156A	0.993
7:16406194:A:G	L134P	0.993
7:16421165:G:T	A53D	0.993
7:16308528:A:G	W262R	0.992
7:16308528:A:T	W262R	0.992
7:16376207:A:T	V190D	0.992
7:16406129:C:G	D156H	0.992
7:16376129:G:T	A216D	0.991
7:16376238:C:G	A180P	0.991
7:16406118:T:A	R159S	0.991
7:16406118:T:G	R159S	0.991

dbSNP variants (sampled 300 via entrez): RS1000004869 (7:16421151 C>A,G,T), RS1000005220 (7:16143435 G>A), RS1000011464 (7:16399698 A>T), RS1000013771 (7:16156601 C>A,G,T), RS1000014711 (7:16308698 C>T), RS1000018520 (7:16221551 C>A,G), RS1000025695 (7:16271667 G>A,C), RS1000033143 (7:16343491 C>A), RS1000054548 (7:16179521 G>A), RS1000057529 (7:16236145 G>A,T), RS1000067582 (7:16397528 C>A,G), RS1000076048 (7:16252044 C>A,G), RS1000085789 (7:16230528 T>C), RS1000095270 (7:16329671 A>G), RS1000099499 (7:16407567 G>A)

Disease associations

OMIM: gene MIM:614631 | disease phenotypes: MIM:614643, MIM:616052, MIM:614830, MIM:613204

GenCC curated gene-disease

Disease	Classification	Inheritance
muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7	Definitive	Autosomal recessive
myopathy caused by variation in CRPPA	Strong	Autosomal recessive
autosomal recessive limb-girdle muscular dystrophy type 2U	Supportive	Autosomal recessive
congenital muscular dystrophy without intellectual disability	Supportive	Autosomal recessive
muscular dystrophy-dystroglycanopathy, type A	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
myopathy caused by variation in CRPPA	Definitive	AR

Mondo (9): muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7 (MONDO:0013835), autosomal recessive limb-girdle muscular dystrophy type 2U (MONDO:0014474), muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8 (MONDO:0013904), muscular dystrophy-dystroglycanopathy (MONDO:0018276), muscular dystrophy (MONDO:0020121), congenital muscular dystrophy due to integrin alpha-7 deficiency (MONDO:0013177), (MONDO:0018279), muscular dystrophy-dystroglycanopathy, type A (MONDO:0000171), myopathy caused by variation in CRPPA (MONDO:0100530)

Orphanet (5): ISPD-related limb-girdle muscular dystrophy R20 (Orphanet:352479), Walker-Warburg syndrome (Orphanet:899), Congenital muscular dystrophy due to dystroglycanopathy (Orphanet:370953), Muscular dystrophy (Orphanet:98473), Congenital muscular dystrophy with integrin alpha-7 deficiency (Orphanet:34520)

HPO phenotypes

128 total (30 of 128 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000158	Macroglossia
HP:0000175	Cleft palate
HP:0000176	Submucous cleft hard palate
HP:0000193	Bifid uvula
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000278	Retrognathia
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000411	Protruding ear
HP:0000478	Abnormality of the eye
HP:0000482	Microcornea
HP:0000486	Strabismus
HP:0000490	Deeply set eye
HP:0000501	Glaucoma
HP:0000505	Visual impairment
HP:0000518	Cataract
HP:0000528	Anophthalmia
HP:0000541	Retinal detachment
HP:0000545	Myopia
HP:0000556	Retinal dystrophy
HP:0000568	Microphthalmia
HP:0000587	Abnormal optic nerve morphology
HP:0000609	Optic nerve hypoplasia
HP:0000612	Iris coloboma
HP:0000648	Optic atrophy
HP:0000659	Peters anomaly

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST001744_3	Serum tamsulosin hydrochloride concentration	4.000000e-07
GCST005956_54	Waist-to-hip ratio adjusted for BMI	4.000000e-06
GCST005959_27	Waist-to-hip ratio adjusted for BMI x sex interaction	7.000000e-06
GCST006979_327	Heel bone mineral density	4.000000e-12
GCST007622_4	Impulsivity	3.000000e-07
GCST007629_1	Impulsivity (non-planning)	9.000000e-08
GCST010536_2	Carotid plaque maximum area	6.000000e-06
GCST010537_4	Mean area of carotid plaque	3.000000e-07
GCST90020026_584	Hip index	2.000000e-10

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008343	sex interaction measurement
EFO:0009270	heel bone mineral density
EFO:0006946	behavioural disinhibition measurement
EFO:0006501	carotid plaque build
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D009136	Muscular Dystrophies	C05.651.534.500; C10.668.491.175.500; C16.320.577
D058494	Walker-Warburg Syndrome	C10.500.507.450.499.249.500; C11.270.881; C16.131.666.507.450.499.249.500; C16.320.577.750
C567709	Muscular Dystrophy, Congenital, Due To Integrin Alpha-7 Deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
lasiocarpine	decreases expression	1
methyleugenol	decreases expression	1
bisphenol A	increases methylation, affects cotreatment	1
ethyl-p-hydroxybenzoate	increases expression	1
tebuconazole	increases expression	1
jinfukang	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Benzo(a)pyrene	decreases expression	1
Cycloheximide	affects response to substance	1
N-Nitrosopyrrolidine	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Okadaic Acid	decreases expression	1

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_ST12	HAP1 ISPD (-) 1	Cancer cell line	Male
CVCL_ST13	HAP1 ISPD (-) 2	Cancer cell line	Male
CVCL_ST14	HAP1 ISPD (-) 3	Cancer cell line	Male
CVCL_ST15	HAP1 ISPD (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01882400	PHASE4	COMPLETED	Assessment of Response to Treatment of Osteoporosis With Oral Bisphosphonates in Patients With Muscular Dystrophy
NCT01254019	PHASE3	COMPLETED	A Clinical Study to Assess the Efficacy and Safety of GSK2402968 in Subjects With Duchenne Muscular Dystrophy
NCT01480245	PHASE3	TERMINATED	Open Label Study of GSK2402968 in Subjects With Duchenne Muscular Dystrophy
NCT01803412	PHASE3	TERMINATED	A Study of the Safety, Tolerability & Efficacy of Long-term Administration of Drisapersen in US & Canadian Subjects
NCT01826487	PHASE3	COMPLETED	Phase 3 Study of Ataluren in Participants With Nonsense Mutation Duchenne Muscular Dystrophy (nmDMD)
NCT01890798	PHASE3	WITHDRAWN	Drisapersen Duchenne Muscular Dystrophy (DMD) Treatment Protocol
NCT02090959	PHASE3	TERMINATED	An Extension Study of Ataluren (PTC124) in Participants With Nonsense Mutation Dystrophinopathy
NCT02432885	PHASE3	COMPLETED	Myocardial Fibrosis Progression in Duchenne and Becker Muscular Dystrophy - ACE Inhibitor Therapy Trial
NCT03179631	PHASE3	COMPLETED	Long-Term Outcomes of Ataluren in Duchenne Muscular Dystrophy
NCT05126758	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Deramiocel (CAP-1002) in Ambulatory and Non-Ambulatory Patients With Duchenne Muscular Dystrophy
NCT07587242	PHASE3	NOT_YET_RECRUITING	A Phase 3 Study to Evaluate the Safety and Efficacy of AOC 1044 (Also Referred to as Delpacibart Zotadirsen) in Participants With DMD With Gene Mutations Amenable to Exon 44 Skipping
NCT07608432	PHASE3	RECRUITING	Efficacy, Safety, and Tolerability of Zeleciment Rostudirsen (DYNE-251) Administered Intravenously Every 4 Weeks in Ambulatory Participants With Duchenne Muscular Dystrophy (FORZETTO)
NCT01153932	PHASE2	COMPLETED	Phase II Doubleblind Exploratory Study of GSK2402968 in Ambulant Subjects With Duchenne Muscular Dystrophy
NCT01462292	PHASE2	COMPLETED	A Clinical Study to Assess Two Doses of GSK2402968 in Subjects With Duchenne Muscular Dystrophy (DMD)
NCT01910649	PHASE2	TERMINATED	A Phase I/II, Open Label, Escalating Dose, Pilot Study to Assess Effect, Safety, Tolerability and PK of Multiple SC Doses of Drisapersen in Patients With Duchenne Muscular Dystrophy and to Assess the Potential for IV Dosing as an Alternative Route of Administration
NCT03406780	PHASE2	COMPLETED	A Study of CAP-1002 in Ambulatory and Non-Ambulatory Patients With Duchenne Muscular Dystrophy
NCT05479981	PHASE2	COMPLETED	Extension of AOC 1001-CS1 (MARINA) Study in Adult Myotonic Dystrophy Type 1 (DM1) Patients
NCT06290713	PHASE2	RECRUITING	Vasodilator and Exercise Study for DMD (VASO-REx)
NCT06547216	PHASE2	ACTIVE_NOT_RECRUITING	Phase 2 Open-label Extension Study of AOC 1020 in Participants With Facioscapulohumeral Muscular Dystrophy (FSHD)
NCT07287189	PHASE2	RECRUITING	Phase 2 Study of SAT-3247 in Pediatric Ambulatory Patients
NCT00494195	PHASE1	COMPLETED	Gene Transfer Therapy for Treating Children and Adults With Limb Girdle Muscular Dystrophy Type 2D (LGMD2D)
NCT00674843	PHASE1	UNKNOWN	The Efficacy of Using Far Infrared Radiation to Manage Muscular Dystrophies
NCT00873782	PHASE1	COMPLETED	Safety Study of Transvenous Limb Perfusion in Human Muscular Dystrophy
NCT01128855	PHASE1	COMPLETED	A Double-blind, Escalating Dose, Randomized, Placebo-controlled Study Assessing PK, Safety, Tolerability in Non-ambulant DMD Subjects
NCT02241928	PHASE1	WITHDRAWN	Stem Cell Therapy in Muscular Dystrophy
NCT03627494	PHASE1	COMPLETED	First Time in Human (FTIH) Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Single and Repeat Doses of GSK3439171A in Healthy Subjects and to Assess Food Effect
NCT05492734	PHASE1	COMPLETED	A Study to Assess the Feasibility of Non-invasive Dried Blood Sampling
NCT05730842	PHASE1	COMPLETED	Absorption, Metabolism, Excretion and Absolute Bioavailability of EDG-5506 in Healthy Volunteers
NCT05989620	Not specified	RECRUITING	Long-Term Development of Muscular Dystrophy Outcome Assessments
NCT04001595	Not specified	UNKNOWN	Global FKRP Registry
NCT01834040	PHASE1/PHASE2	UNKNOWN	Study Safety and Efficacy of BMMNC for the Patient With Duchenne Muscular Dystrophy
NCT01834066	PHASE1/PHASE2	UNKNOWN	Study Safety and Efficacy of Bone Marrow Derived Autologous Cells for the Treatment of Muscular Dystrophy.
NCT02515669	PHASE1/PHASE2	TERMINATED	Study of an Investigational Drug, RO7239361 (BMS-986089), in Ambulatory Boys With DMD
NCT05230459	PHASE1/PHASE2	RECRUITING	A Study to Evaluate the Safety of AB-1003 (Previously LION-101) in Subjects With Genetic Confirmation of LGMD2I/R9 (Part1)
NCT05747924	PHASE1/PHASE2	COMPLETED	Phase 1/2 Study of AOC 1020 in Participants With Facioscapulohumeral Muscular Dystrophy (FSHD)
NCT02653833	EARLY_PHASE1	TERMINATED	The Study of Skeletal Muscle Blood Flow in Becker Muscular Dystrophy
NCT00001164	Not specified	COMPLETED	Studies of Patients With Skin Disease, Patients With Neurological Degenerations, and Normal Volunteers
NCT00004568	Not specified	RECRUITING	Study of Inherited Neurological Disorders
NCT00027391	Not specified	COMPLETED	Study of Albuterol and Oxandrolone in Patients With Facioscapulohumeral Dystrophy (FSHD)
NCT00082108	Not specified	RECRUITING	Myotonic Dystrophy and Facioscapulohumeral Muscular Dystrophy Registry