TRAPPC11

Summary

TRAPPC11 (trafficking protein particle complex subunit 11, HGNC:25751) is a protein-coding gene on chromosome 4q35.1, encoding Trafficking protein particle complex subunit 11 (Q7Z392). Involved in endoplasmic reticulum to Golgi apparatus trafficking at a very early stage. It is a common-essential gene (DepMap: required in 97.2% of cancer cell lines).

The protein encoded by this gene is a subunit of the TRAPP (transport protein particle) tethering complex, which functions in intracellular vesicle trafficking. This subunit is involved in early stage endoplasmic reticulum-to-Golgi vesicle transport. Alternative splicing of this gene results in multiple transcript variants.

Source: NCBI Gene 60684 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal recessive limb-girdle muscular dystrophy (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 1,011 total — 34 pathogenic, 23 likely-pathogenic
• Phenotypes (HPO): 89
• Cancer dependency (DepMap): dependent in 97.2% of screened cell lines (common-essential)
• MANE Select transcript: NM_021942

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25751
Approved symbol	TRAPPC11
Name	trafficking protein particle complex subunit 11
Location	4q35.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ12716, gry, foigr
Ensembl gene	ENSG00000168538
Ensembl biotype	protein_coding
OMIM	614138
Entrez	60684

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 12 protein_coding, 4 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000334690, ENST00000357207, ENST00000504526, ENST00000505676, ENST00000506426, ENST00000509857, ENST00000511409, ENST00000511955, ENST00000512476, ENST00000513600, ENST00000878953, ENST00000878954, ENST00000878955, ENST00000878956, ENST00000917116, ENST00000917118, ENST00000917119, ENST00000965355, ENST00000965356

RefSeq mRNA: 2 — MANE Select: NM_021942 NM_021942, NM_199053

CCDS: CCDS34112, CCDS47166

Canonical transcript exons

ENST00000334690 — 30 exons

Exon	Start	End
ENSE00001150055	183684696	183684841
ENSE00001171163	183686618	183686748
ENSE00001171173	183685271	183685403
ENSE00001171182	183685084	183685145
ENSE00001171189	183684305	183684359
ENSE00001171198	183684145	183684223
ENSE00001171206	183683975	183684054
ENSE00001171608	183679353	183679486
ENSE00001171613	183677458	183677554
ENSE00001199932	183682732	183682825
ENSE00001219976	183680120	183680267
ENSE00001630075	183712600	183713589
ENSE00003470181	183675164	183675237
ENSE00003476628	183674713	183674812
ENSE00003487139	183667060	183667130
ENSE00003500576	183697503	183697568
ENSE00003501305	183701697	183701808
ENSE00003512572	183694604	183694723
ENSE00003514685	183704979	183705070
ENSE00003538534	183708407	183708574
ENSE00003571669	183663847	183664071
ENSE00003601156	183706807	183706940
ENSE00003606550	183697679	183697835
ENSE00003610027	183692960	183693147
ENSE00003637239	183691316	183691471
ENSE00003646329	183693917	183694038
ENSE00003647760	183666257	183666426
ENSE00003653571	183693589	183693737
ENSE00003653884	183668003	183668117
ENSE00003850025	183659293	183659447

Expression profiles

Bgee: expression breadth ubiquitous, 277 present calls, max score 95.30.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.5549 / max 208.2473, expressed in 1812 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
50797	18.1804	1810
50798	2.3717	1264
203441	0.0028	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	95.30	gold quality
adrenal tissue	UBERON:0018303	92.36	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.62	gold quality
monocyte	CL:0000576	91.43	gold quality
mononuclear cell	CL:0000842	91.24	gold quality
leukocyte	CL:0000738	90.92	gold quality
ventricular zone	UBERON:0003053	90.13	gold quality
right adrenal gland cortex	UBERON:0035827	89.80	gold quality
right adrenal gland	UBERON:0001233	89.69	gold quality
cerebellar hemisphere	UBERON:0002245	89.67	gold quality
right ovary	UBERON:0002118	89.65	gold quality
left ovary	UBERON:0002119	89.61	gold quality
cerebellar cortex	UBERON:0002129	89.59	gold quality
right hemisphere of cerebellum	UBERON:0014890	89.46	gold quality
tonsil	UBERON:0002372	89.34	gold quality
visceral pleura	UBERON:0002401	89.13	gold quality
left adrenal gland	UBERON:0001234	89.11	gold quality
left adrenal gland cortex	UBERON:0035825	89.08	gold quality
adrenal gland	UBERON:0002369	89.03	gold quality
ovary	UBERON:0000992	88.94	gold quality
tendon	UBERON:0000043	88.90	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.85	gold quality
cerebellum	UBERON:0002037	88.64	gold quality
parietal pleura	UBERON:0002400	88.60	gold quality
adrenal cortex	UBERON:0001235	88.34	gold quality
stromal cell of endometrium	CL:0002255	88.29	gold quality
cortical plate	UBERON:0005343	88.18	gold quality
choroid plexus epithelium	UBERON:0003911	88.16	gold quality
ganglionic eminence	UBERON:0004023	87.95	gold quality
germinal epithelium of ovary	UBERON:0001304	87.86	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.70

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

34 targeting TRAPPC11, 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-4282	99.99	75.36	6408
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-2681-5P	99.75	67.64	1655
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-548AV-3P	99.43	68.50	1721
HSA-MIR-330-3P	99.41	69.95	2521
HSA-MIR-4427	99.34	70.33	1854
HSA-MIR-6719-3P	99.29	67.78	1387
HSA-MIR-5584-3P	99.23	68.79	1351
HSA-MIR-3925-5P	99.21	67.90	1466
HSA-MIR-499A-3P	99.18	69.20	1392
HSA-MIR-499B-3P	99.18	69.27	1391
HSA-MIR-146A-3P	99.13	68.99	1881
HSA-MIR-376A-3P	99.06	69.17	1128
HSA-MIR-376B-3P	99.06	69.17	1128
HSA-MIR-4738-3P	98.98	67.98	1846
HSA-MIR-3145-3P	98.85	69.07	2031
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-11399	98.71	65.69	869
HSA-MIR-4680-3P	98.64	68.60	2093

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 97.2% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 7)

• Homozygous mutations in the membrane trafficking component TRAPPC11 causes a form of autosomal-recessive, slowly progressive limb girdle muscular dystrophy with childhood onset and high serum creatine kinase. (PMID:23830518)
• TRAPPC11 role in protein glycosylation and lipid-linked oligosaccharides biosynthesis (PMID:26912795)
• The identified novel TRAPPC11 mutation represents an expansion of the myopathy phenotype described before and is characterised particularly by achalasia, alacrima, neurological and muscular phenotypes. (PMID:27707803)
• Recessive mutations in TRAPPC11 and GOSR2 are associated with congenital muscular dystrophy and hypoglycosylation of alpha-dystroglycan. (PMID:29855340)
• TRAPPC11 recruits ATG2B-WIPI4/WDR45 to preautophagosomal membranes. Fibroblasts from a patient with TRAPPC11 mutations failed to recruit ATG2B-WIPI4. (PMID:30843302)
• Expanding the phenotypic spectrum of TRAPPC11-related muscular dystrophy: 25 Roma individuals carrying a founder variant. (PMID:37197784)
• Large TRAPPC11 gene deletions as a cause of muscular dystrophy and their estimated genesis. (PMID:38955476)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	trappc11	ENSDARG00000004726
mus_musculus	Trappc11	ENSMUSG00000038102
rattus_norvegicus	Trappc11	ENSRNOG00000022482
drosophila_melanogaster	gry	FBGN0286567
caenorhabditis_elegans		WBGENE00015173

Protein

Protein identifiers

Trafficking protein particle complex subunit 11 — Q7Z392 (reviewed: Q7Z392)

All UniProt accessions (3): Q7Z392, D6R9T9, D6RHE5

UniProt curated annotations — full annotation on UniProt →

Function. Involved in endoplasmic reticulum to Golgi apparatus trafficking at a very early stage.

Subunit / interactions. Component of the multisubunit TRAPP (transport protein particle) complex, which includes at least TRAPPC2, TRAPPC2L, TRAPPC3, TRAPPC3L, TRAPPC4, TRAPPC5, TRAPPC8, TRAPPC9, TRAPPC10, TRAPPC11 and TRAPPC12.

Subcellular location. Golgi apparatus. cis-Golgi network.

Disease relevance. Muscular dystrophy, limb-girdle, autosomal recessive 18 (LGMDR18) [MIM:615356] A form of limb-girdle muscular dystrophy characterized by proximal muscle weakness with childhood onset, resulting in gait abnormalities and scapular winging. Serum creatine kinase is increased. A subset of patients may show a hyperkinetic movement disorder with chorea, ataxia, or dystonia and global developmental delay. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the TRAPPC11 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q7Z392-1	1	yes
Q7Z392-2	2
Q7Z392-3	3
Q7Z392-4	4

RefSeq proteins (2): NP_068761, NP_951008 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR021773	TPC11	Domain
IPR025876	TRAPPC11_C	Domain

Pfam: PF11817, PF12742

UniProt features (28 total): sequence conflict 17, splice variant 5, sequence variant 4, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z392-F1	87.76	0.56

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): 245

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8876198	RAB GEFs exchange GTP for GDP on RABs

MSigDB gene sets: 274 (showing top): GOBP_VESICLE_LOCALIZATION, XU_GH1_AUTOCRINE_TARGETS_UP, GOBP_VESICLE_ORGANIZATION, GOBP_VESICLE_TARGETING, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, GOBP_EXOCYTOSIS, GOBP_ENDOPLASMIC_RETICULUM_TO_GOLGI_VESICLE_MEDIATED_TRANSPORT, chr4q35, GOBP_SECRETION, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, TURASHVILI_BREAST_DUCTAL_CARCINOMA_VS_DUCTAL_NORMAL_DN, RYTTCCTG_ETS2_B, ELK1_01, GOBP_MEMBRANE_ORGANIZATION

GO Biological Process (7): endoplasmic reticulum to Golgi vesicle-mediated transport (GO:0006888), Golgi organization (GO:0007030), constitutive secretory pathway (GO:0045054), COPII vesicle coat assembly (GO:0048208), regulation of protein complex stability (GO:0061635), obsolete vesicle tethering (GO:0099022), vesicle-mediated transport (GO:0016192)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (5): cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), cytosol (GO:0005829), TRAPP complex (GO:0030008), TRAPPIII protein complex (GO:1990072)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Rab regulation of trafficking	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	3
cellular anatomical structure	2
intercellular transport	1
intracellular transport	1
Golgi vesicle transport	1
organelle organization	1
endomembrane system organization	1
exocytosis	1
vesicle coat assembly	1
protein-containing complex assembly	1
COPII-coated vesicle budding	1
regulation of biological quality	1
transport	1
cellular process	1
binding	1
intracellular anatomical structure	1
endomembrane system	1
intracellular membrane-bounded organelle	1
vesicle tethering complex	1
intracellular protein-containing complex	1
Golgi apparatus	1
TRAPP complex	1

Protein interactions and networks

STRING

1270 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRAPPC11	TRAPPC12	Q8WVT3	984
TRAPPC11	TRAPPC8	Q9Y2L5	971
TRAPPC11	TRAPPC13	A5PLN9	964
TRAPPC11	TRAPPC2	P0DI81	852
TRAPPC11	TRAPPC2L	Q9UL33	811
TRAPPC11	TRAPPC3	O43617	808
TRAPPC11	TRAPPC9	Q96Q05	772
TRAPPC11	TRAPPC4	Q9Y296	771
TRAPPC11	TRAPPC1	Q9Y5R8	751
TRAPPC11	TRAPPC5	Q8IUR0	744
TRAPPC11	TRAPPC10	P48553	742
TRAPPC11	TRAPPC6B	Q86SZ2	715
TRAPPC11	TRAPPC6A	O75865	710
TRAPPC11	GOSR2	O14653	624
TRAPPC11	GMPPB	Q9Y5P6	568

IntAct

39 interactions, top by confidence:

A	B	Type	Score
TRAPPC2L	TRAPPC13	psi-mi:“MI:0914”(association)	0.560
TRAPPC12	TRAPPC3	psi-mi:“MI:0914”(association)	0.530
TRAPPC1	TRAPPC13	psi-mi:“MI:0914”(association)	0.530
TRAPPC11	KRT8	psi-mi:“MI:0915”(physical association)	0.400
RACGAP1	STX18	psi-mi:“MI:0914”(association)	0.350
Trappc8	TRAPPC13	psi-mi:“MI:0914”(association)	0.350
ALB	CNOT1	psi-mi:“MI:0914”(association)	0.350
	TRAPPC13	psi-mi:“MI:0914”(association)	0.350
TRAPPC5	TRAPPC13	psi-mi:“MI:0914”(association)	0.350
TBC1D14		psi-mi:“MI:0914”(association)	0.350
TRAPPC1	TRAPPC13	psi-mi:“MI:0914”(association)	0.350
TECPR1	PLOD3	psi-mi:“MI:0914”(association)	0.350
ARL6IP6	ARPC1B	psi-mi:“MI:0914”(association)	0.350
TRAPPC11	TRAPPC13	psi-mi:“MI:0914”(association)	0.350
TRAPPC2	TRAPPC13	psi-mi:“MI:0914”(association)	0.350
trappc2_trappc2b_human	TRAPPC13	psi-mi:“MI:0914”(association)	0.350
CMBL	TRAPPC13	psi-mi:“MI:0914”(association)	0.350
TBC1D14	TRAPPC13	psi-mi:“MI:0914”(association)	0.350
RAB43	TRAPPC13	psi-mi:“MI:0914”(association)	0.350
OTUB2	TRAPPC13	psi-mi:“MI:0914”(association)	0.350
GAB2	TRAPPC13	psi-mi:“MI:0914”(association)	0.350
TRAPPC6B	TRAPPC13	psi-mi:“MI:0914”(association)	0.350
TRAPPC12	TRAPPC13	psi-mi:“MI:0914”(association)	0.350

BioGRID (133): TRAPPC11 (Affinity Capture-MS), TRAPPC11 (Affinity Capture-MS), TRAPPC11 (Affinity Capture-MS), TRAPPC11 (Affinity Capture-MS), TRAPPC11 (Synthetic Lethality), TRAPPC11 (Affinity Capture-MS), TRAPPC11 (Affinity Capture-MS), TRAPPC11 (Affinity Capture-MS), TRAPPC11 (Affinity Capture-MS), TRAPPC11 (Affinity Capture-MS), TRAPPC11 (Negative Genetic), TRAPPC11 (Negative Genetic), TRAPPC11 (Negative Genetic), TRAPPC11 (Negative Genetic), TRAPPC11 (Negative Genetic)

ESM2 similar proteins: A0A0G2K344, D3ZGS3, F1M386, F1MSG6, F1PBJ0, G5EF51, O00329, O02697, O35242, O35904, O70481, O88763, O94830, P32871, P42336, P42337, P42338, P42339, P42347, P42348, P48736, P50520, P54676, P70600, Q01968, Q14289, Q14BI7, Q16JS8, Q3MHU3, Q3UYK3, Q4KWH5, Q4KWH8, Q5D891, Q5ZI89, Q6AZN6, Q6GQ76, Q6NVF0, Q6PF93, Q7Z392, Q80Y98

Diamond homologs: A6QLC7, B2RXC1, Q1RLX4, Q5ZI89, Q7Z392

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
TRAPPC11	“form complex”	“TRAPP III complex, TRAPPC2 variant”	binding
TRAPPC11	“form complex”	“TRAPP III complex, TRAPPC2B variant”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 31 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
COPII-mediated vesicle transport	7	43.9×	8e-09
RAB GEFs exchange GTP for GDP on RABs	8	38.2×	2e-09

GO biological processes:

GO term	Partners	Fold	FDR
obsolete vesicle tethering	8	305.0×	3e-17
COPII vesicle coat assembly	6	162.0×	3e-11
endoplasmic reticulum to Golgi vesicle-mediated transport	10	52.3×	6e-14

Disease & clinical

Clinical variants and AI predictions

ClinVar

1011 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	34
Likely pathogenic	23
Uncertain significance	423
Likely benign	375
Benign	87

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1033578	NM_021942.6(TRAPPC11):c.2625del (p.His875fs)	Pathogenic
1323707	NM_021942.6(TRAPPC11):c.2579del (p.Leu860fs)	Pathogenic
1425984	NM_021942.6(TRAPPC11):c.630_631del (p.His210fs)	Pathogenic
1429017	NM_021942.6(TRAPPC11):c.1381G>T (p.Glu461Ter)	Pathogenic
1454783	NM_021942.6(TRAPPC11):c.1051C>T (p.Gln351Ter)	Pathogenic
1456744	NC_000004.11:g.(?184622830)(184633797_?)del	Pathogenic
1457515	NM_021942.6(TRAPPC11):c.1291_1297del (p.Glu430_Ile431insTer)	Pathogenic
1972684	NM_021942.6(TRAPPC11):c.171_174dup (p.Asp59delinsArgTer)	Pathogenic
2041292	NM_021942.6(TRAPPC11):c.886C>T (p.Arg296Ter)	Pathogenic
2135671	NM_021942.6(TRAPPC11):c.370del (p.Val124fs)	Pathogenic
2141268	NM_021942.6(TRAPPC11):c.913_914del (p.Lys305fs)	Pathogenic
2230005	NM_021942.6(TRAPPC11):c.1190G>A (p.Trp397Ter)	Pathogenic
2418901	NM_021942.6(TRAPPC11):c.1702C>T (p.Arg568Ter)	Pathogenic
2426695	NC_000004.11:g.(?184585021)(184585244_?)del	Pathogenic
268054	NM_021942.6(TRAPPC11):c.661-1G>T	Pathogenic
268055	NM_021942.6(TRAPPC11):c.1893+3A>G	Pathogenic
2729079	NM_021942.6(TRAPPC11):c.2173del (p.Arg725fs)	Pathogenic
2756727	NM_021942.6(TRAPPC11):c.1816C>T (p.Gln606Ter)	Pathogenic
2810365	NM_021942.6(TRAPPC11):c.1131del (p.Asn378fs)	Pathogenic
2850813	NM_021942.6(TRAPPC11):c.666_669del (p.Phe223fs)	Pathogenic
2858941	NM_021942.6(TRAPPC11):c.725del (p.Asn242fs)	Pathogenic
3246687	NC_000004.11:g.(?184615786)(184627497_?)del	Pathogenic
3611604	NM_021942.6(TRAPPC11):c.3239del (p.Phe1080fs)	Pathogenic
3706830	NM_021942.6(TRAPPC11):c.2760del (p.Ser921fs)	Pathogenic
375391	NM_021942.6(TRAPPC11):c.142C>T (p.Arg48Ter)	Pathogenic
3769102	NC_000004.11:g.(184622962_184626131)_(184626224_184627959)del	Pathogenic
450724	NM_021942.6(TRAPPC11):c.2168dup (p.Lys724fs)	Pathogenic
4710613	NM_021942.6(TRAPPC11):c.1234_1237del (p.Glu412fs)	Pathogenic
4734414	NM_021942.6(TRAPPC11):c.61dup (p.Thr21fs)	Pathogenic
4735217	NM_021942.6(TRAPPC11):c.766G>T (p.Glu256Ter)	Pathogenic

SpliceAI

4877 predictions. Top by Δscore:

Variant	Effect	Δscore
4:183666255:A:AG	acceptor_gain	1.0000
4:183666256:G:GG	acceptor_gain	1.0000
4:183666256:GA:G	acceptor_gain	1.0000
4:183666422:GTCAG:G	donor_gain	1.0000
4:183666423:TCAG:T	donor_loss	1.0000
4:183666424:CAGG:C	donor_loss	1.0000
4:183666426:GGTA:G	donor_loss	1.0000
4:183666427:GTATG:G	donor_loss	1.0000
4:183666428:T:A	donor_loss	1.0000
4:183667053:A:AG	acceptor_gain	1.0000
4:183667056:GCAG:G	acceptor_loss	1.0000
4:183667057:CA:C	acceptor_loss	1.0000
4:183667058:A:AG	acceptor_gain	1.0000
4:183667058:A:T	acceptor_loss	1.0000
4:183667058:AG:A	acceptor_gain	1.0000
4:183667059:G:GC	acceptor_gain	1.0000
4:183667059:GG:G	acceptor_gain	1.0000
4:183667059:GGC:G	acceptor_gain	1.0000
4:183667059:GGCA:G	acceptor_gain	1.0000
4:183667059:GGCAA:G	acceptor_gain	1.0000
4:183667126:CCCAG:C	donor_loss	1.0000
4:183667127:CCAG:C	donor_loss	1.0000
4:183667128:CAG:C	donor_loss	1.0000
4:183667129:AG:A	donor_loss	1.0000
4:183667130:GGTAT:G	donor_loss	1.0000
4:183667131:G:C	donor_loss	1.0000
4:183667132:T:A	donor_loss	1.0000
4:183667984:T:A	acceptor_gain	1.0000
4:183667988:G:A	acceptor_gain	1.0000
4:183674701:T:TA	acceptor_gain	1.0000

AlphaMissense

7452 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:183663926:T:A	V20D	1.000
4:183663932:T:C	L22P	1.000
4:183663941:T:C	L25P	1.000
4:183666305:T:A	W85R	1.000
4:183666305:T:C	W85R	1.000
4:183666307:G:C	W85C	1.000
4:183666307:G:T	W85C	1.000
4:183666333:C:A	P94Q	1.000
4:183666333:C:G	P94R	1.000
4:183666365:T:A	W105R	1.000
4:183666365:T:C	W105R	1.000
4:183666367:G:C	W105C	1.000
4:183666367:G:T	W105C	1.000
4:183667098:T:A	V138D	1.000
4:183667101:T:C	L139P	1.000
4:183668078:T:A	V174E	1.000
4:183668081:T:C	L175P	1.000
4:183668104:G:C	G183R	1.000
4:183668105:G:A	G183D	1.000
4:183675177:G:T	R225M	1.000
4:183675190:A:C	K229N	1.000
4:183675190:A:T	K229N	1.000
4:183679408:G:C	R296P	1.000
4:183679473:T:A	W318R	1.000
4:183679473:T:C	W318R	1.000
4:183680134:G:A	G327E	1.000
4:183684172:G:C	A439P	1.000
4:183708570:T:A	V1118D	1.000
4:183663937:G:C	G24R	0.999
4:183663941:T:A	L25Q	0.999

dbSNP variants (sampled 300 via entrez): RS1000005380 (4:183699509 A>G), RS1000034898 (4:183699131 G>A), RS1000099024 (4:183658427 T>C), RS1000116191 (4:183676140 C>T), RS1000132142 (4:183672501 G>A), RS1000269077 (4:183682469 A>G), RS1000364301 (4:183669848 G>C), RS1000380004 (4:183710382 G>A), RS1000638838 (4:183672606 T>C), RS1000649741 (4:183694113 G>A,T), RS1000689841 (4:183672103 C>T), RS1000799100 (4:183669724 C>T), RS1000938610 (4:183706282 G>A), RS1001037971 (4:183696992 C>T), RS1001164086 (4:183660840 A>G,T)

Disease associations

OMIM: gene MIM:614138 | disease phenotypes: MIM:615356, MIM:253600, MIM:618138

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal recessive limb-girdle muscular dystrophy type R18	Definitive	Autosomal recessive
intellectual disability-hyperkinetic movement-truncal ataxia syndrome	Supportive	Autosomal recessive
triple-A syndrome	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
autosomal recessive limb-girdle muscular dystrophy	Definitive	AR

Mondo (8): autosomal recessive limb-girdle muscular dystrophy type R18 (MONDO:0014144), autosomal recessive limb-girdle muscular dystrophy (MONDO:0015152), limb-girdle muscular dystrophy (MONDO:0016971), myopathy (MONDO:0005336), muscular dystrophy (MONDO:0020121), muscular dystrophy, limb-girdle, autosomal recessive 23 (MONDO:0029136), intellectual disability-hyperkinetic movement-truncal ataxia syndrome (MONDO:0018243), triple-A syndrome (MONDO:0009279)

Orphanet (5): Autosomal recessive limb-girdle muscular dystrophy (Orphanet:102015), TRAPPC11-related limb-girdle muscular dystrophy R18 (Orphanet:369840), Limb-girdle muscular dystrophy (Orphanet:263), Muscular dystrophy (Orphanet:98473), Laminin subunit alpha 2-related limb-girdle muscular dystrophy R23 (Orphanet:565837)

HPO phenotypes

89 total (30 of 89 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000407	Sensorineural hearing impairment
HP:0000486	Strabismus
HP:0000505	Visual impairment
HP:0000518	Cataract
HP:0000522	Alacrima
HP:0000545	Myopia
HP:0000648	Optic atrophy
HP:0000846	Adrenal insufficiency
HP:0000982	Palmoplantar keratoderma
HP:0001097	Keratoconjunctivitis sicca
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001265	Hyporeflexia
HP:0001272	Cerebellar atrophy
HP:0001288	Gait disturbance
HP:0001290	Generalized hypotonia
HP:0001332	Dystonia
HP:0001337	Tremor
HP:0001344	Absent speech
HP:0001347	Hyperreflexia
HP:0001385	Hip dysplasia
HP:0001397	Hepatic steatosis
HP:0001511	Intrauterine growth retardation
HP:0001531	Failure to thrive in infancy

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST005754_3	Systemic lupus erythematosus	1.000000e-14

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D009136	Muscular Dystrophies	C05.651.534.500; C10.668.491.175.500; C16.320.577
D049288	Muscular Dystrophies, Limb-Girdle	C05.651.534.500.280; C10.668.491.175.500.149; C16.320.577.280
C536008	Achalasia Addisonianism Alacrimia syndrome (supp.)
C538640	Limb-girdle muscular dystrophy autosomal recessive (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, decreases methylation	6
potassium chromate(VI)	affects cotreatment, decreases expression	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
Arsenic	decreases methylation, increases abundance, affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	decreases expression, increases abundance, affects cotreatment	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
chromium hexavalent ion	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Leflunomide	increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants, Occupational	decreases expression	1
Manganese	decreases expression, increases abundance, affects cotreatment	1
Nickel	decreases expression	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Quercetin	decreases expression	1
Cyclosporine	increases expression	1
Uranium Compounds	decreases expression	1
Metals, Heavy	decreases methylation, increases abundance	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00120055	PHASE4	COMPLETED	Association Between Systemic Exposure of Atorvastatin and Metabolites and Atorvastatin-induced Myotoxicity
NCT03633565	PHASE4	UNKNOWN	Comparative Study of Strategies for Management of Duchenne Myopathy (DM)
NCT01882400	PHASE4	COMPLETED	Assessment of Response to Treatment of Osteoporosis With Oral Bisphosphonates in Patients With Muscular Dystrophy
NCT03783923	PHASE3	TERMINATED	A Study of Deflazacort (Emflaza®) in Participants With Limb-Girdle Muscular Dystrophy 2I (LGMD2I)
NCT06246513	PHASE3	ACTIVE_NOT_RECRUITING	A Trial to Learn More About an Experimental Gene Therapy Called Bidridistrogene Xeboparvovec (SRP-9003) as a Possible Treatment for Limb Girdle Muscular Dystrophy 2E/R4
NCT01225614	PHASE3	UNKNOWN	Efficacy and Tolerance of Early Launching of Nocturnal Non Invasive
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)
NCT04054375	PHASE2	COMPLETED	Weekly Steroids in Muscular Dystrophy
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
NCT00873782	PHASE1	COMPLETED	Safety Study of Transvenous Limb Perfusion in Human Muscular Dystrophy
NCT01344798	PHASE1	COMPLETED	Clinical Study of AAV1-gamma-sarcoglycan Gene Therapy for Limb Girdle Muscular Dystrophy Type 2C
NCT02050776	PHASE1	WITHDRAWN	Stem Cell Therapy in Limb Girdle Muscular Dystrophy
NCT02245711	PHASE1	WITHDRAWN	Cell Therapy in Limb Girdle Muscular Dystrophy
NCT05876780	PHASE1	ACTIVE_NOT_RECRUITING	A Gene Transfer Single Dose Study to Evaluate the Safety, Tolerability and Efficacy of SRP-9003 in Non-Ambulatory and Ambulatory Participants With Limb Girdle Muscular Dystrophy, Type 2E/R4 (Beta-Sarcoglycan [β-SG] Deficiency)
NCT05906251	PHASE1	TERMINATED	A Gene Transfer Study to Evaluate the Safety, Tolerability and Efficacy of SRP-6004 in Ambulatory Participants With Limb Girdle Muscular Dystrophy, Type 2B/R2 (LGMD2B/R2, Dysferlin [DYSF] Related)
NCT06747273	PHASE1	TERMINATED	Study to Evaluate the Safety, Tolerability, and Efficacy of SRP-9004 Administered by Systemic Infusion in Limb Girdle Muscular Dystrophy Type 2D/R3 Participants in the United States
NCT00278564	PHASE1	TERMINATED	Stem Cell Transplantation in Idiopathic Inflammatory Myopathy Diseases
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
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