RXYLT1

Summary

RXYLT1 (ribitol xylosyltransferase 1, HGNC:13530) is a protein-coding gene on chromosome 12q14.2, encoding Ribitol-5-phosphate xylosyltransferase 1 (Q9Y2B1). Acts as a UDP-D-xylose:ribitol-5-phosphate beta1,4-xylosyltransferase, which catalyzes the transfer of UDP-D-xylose to ribitol 5-phosphate (Rbo5P) to form the Xylbeta1-4Rbo5P linkage on O-mannosyl glycan.

This gene encodes a type II transmembrane protein that is thought to have glycosyltransferase function. Mutations in this gene result in cobblestone lissencephaly. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 10329 — RefSeq curated summary.

At a glance

• Gene–disease (curated): muscle-eye-brain disease (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 450 total — 36 pathogenic, 11 likely-pathogenic
• Phenotypes (HPO): 56
• MANE Select transcript: NM_014254

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13530
Approved symbol	RXYLT1
Name	ribitol xylosyltransferase 1
Location	12q14.2
Locus type	gene with protein product
Status	Approved
Aliases	HP10481
Ensembl gene	ENSG00000118600
Ensembl biotype	protein_coding
OMIM	605862
Entrez	10329

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 8 nonsense_mediated_decay, 5 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined, 1 TEC

ENST00000261234, ENST00000433461, ENST00000535963, ENST00000536219, ENST00000537373, ENST00000537982, ENST00000543342, ENST00000623171, ENST00000685296, ENST00000687087, ENST00000690060, ENST00000691840, ENST00000692910, ENST00000693579, ENST00000894951, ENST00000930426, ENST00000947510, ENST00000947511

RefSeq mRNA: 2 — MANE Select: NM_014254 NM_001278237, NM_014254

CCDS: CCDS8966

Canonical transcript exons

ENST00000261234 — 6 exons

Exon	Start	End
ENSE00000799596	63808675	63809562
ENSE00002232584	63779909	63780129
ENSE00003468673	63805234	63805404
ENSE00003540485	63802091	63802405
ENSE00003551977	63781019	63781174
ENSE00003634895	63784970	63785072

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 94.76.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.3226 / max 256.4167, expressed in 1805 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
126411	7.2839	1755
126412	5.0640	1681
126414	4.4740	1624
126413	1.5007	1083

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus epididymis	UBERON:0004359	94.76	gold quality
caput epididymis	UBERON:0004358	94.42	gold quality
cranial nerve II	UBERON:0000941	94.04	gold quality
mammary duct	UBERON:0001765	93.28	gold quality
gluteal muscle	UBERON:0002000	93.11	gold quality
epithelium of mammary gland	UBERON:0003244	92.61	gold quality
pericardium	UBERON:0002407	91.99	gold quality
cauda epididymis	UBERON:0004360	91.95	gold quality
renal medulla	UBERON:0000362	90.75	gold quality
tibia	UBERON:0000979	90.70	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	90.52	gold quality
superior surface of tongue	UBERON:0007371	90.32	gold quality
islet of Langerhans	UBERON:0000006	90.18	gold quality
parietal pleura	UBERON:0002400	90.17	gold quality
calcaneal tendon	UBERON:0003701	90.02	gold quality
bronchial epithelial cell	CL:0002328	89.82	gold quality
bronchus	UBERON:0002185	89.54	gold quality
nipple	UBERON:0002030	89.48	gold quality
epithelium of bronchus	UBERON:0002031	89.48	gold quality
saphenous vein	UBERON:0007318	89.44	gold quality
pleura	UBERON:0000977	89.41	gold quality
lower lobe of lung	UBERON:0008949	88.88	gold quality
trachea	UBERON:0003126	88.79	gold quality
tongue	UBERON:0001723	88.78	gold quality
germinal epithelium of ovary	UBERON:0001304	88.72	gold quality
visceral pleura	UBERON:0002401	88.52	gold quality
pylorus	UBERON:0001166	88.43	gold quality
adrenal cortex	UBERON:0001235	88.33	gold quality
mammary gland	UBERON:0001911	88.33	gold quality
thoracic mammary gland	UBERON:0005200	88.28	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.33

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

37 targeting RXYLT1, 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-8485	100.00	77.57	4731
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-3913-3P	99.74	66.53	938
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-5689	99.50	71.26	1154
HSA-MIR-580-5P	99.28	70.94	1776
HSA-MIR-4528	99.18	69.77	1936
HSA-MIR-3688-5P	99.12	69.67	1091
HSA-MIR-548L	99.06	70.90	2560
HSA-MIR-5701	98.97	69.54	1502
HSA-MIR-513B-3P	98.76	68.12	1577
HSA-MIR-3908	98.75	67.31	1160
HSA-MIR-4718	98.55	68.61	814
HSA-MIR-4439	98.53	67.53	793
HSA-MIR-3136-5P	98.53	67.68	793
HSA-MIR-302F	98.44	69.02	1776
HSA-MIR-3130-5P	98.14	66.00	711

Literature-anchored findings (GeneRIF, showing 5)

• TMEM5 mutations were frequently associated with gonadal dysgenesis and neural tube defects, and ISPD mutations were frequently associated with brain vascular anomalies. (PMID:23217329)
• TMEM5 is a UDP-xylosyl transferase that elaborates the O-mannose glycan structure on alpha-dystroglycan. The authors demonstrate in a zebrafish model as well as in a human patient that defects in TMEM5 result in muscular dystrophy in combination with abnormal brain development. (PMID:27130732)
• TMEM5 acts as a UDP-d-xylose:ribitol-5-phosphate beta1,4-xylosyltransferase in the biosynthetic pathway of O-mannosyl glycan. (PMID:27733679)
• Fukutin, FKRP, and TMEM5 form a complex while maintaining each of their enzyme activities. Data showed that endogenous fukutin and FKRP enzyme activities coexist with TMEM5 enzyme activity, and suggest the possibility that formation of this enzyme complex may contribute to specific and prompt biosynthesis of glycans that are required for dystroglycan function. (PMID:29477842)
• RETINAL MANIFESTATIONS OF WALKER-WARBURG SYNDROME IN TWO SIBLINGS WITH RXYLT1 MUTATIONS. (PMID:36007194)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rxylt1	ENSDARG00000063414
mus_musculus	Rxylt1	ENSMUSG00000034620
rattus_norvegicus	Rxylt1	ENSRNOG00000004421

Protein

Protein identifiers

Ribitol-5-phosphate xylosyltransferase 1 — Q9Y2B1 (reviewed: Q9Y2B1)

Alternative names: Transmembrane protein 5, UDP-D-xylose:ribitol-5-phosphate beta1,4-xylosyltransferase

All UniProt accessions (6): Q9Y2B1, A0A8I5KTH6, A0A8I5KWX9, A0A8I5QJ99, F5GXF8, G3V1K2

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a UDP-D-xylose:ribitol-5-phosphate beta1,4-xylosyltransferase, which catalyzes the transfer of UDP-D-xylose to ribitol 5-phosphate (Rbo5P) to form the Xylbeta1-4Rbo5P linkage on O-mannosyl glycan. Participates in 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.

Subunit / interactions. Forms a complex composed of FKTN/fukutin, FKRP and RXYLT1/TMEM5.

Subcellular location. Golgi apparatus membrane.

Disease relevance. Muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A10 (MDDGA10) [MIM:615041] 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.

Pathway. Protein modification; protein glycosylation.

Similarity. Belongs to the RXYLT1 family.

RefSeq proteins (2): NP_001265166, NP_055069* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR055286	RXYLT1-like	Family
IPR057538	RXYLT1_C	Domain
IPR057539	RXYLT1_N	Domain

Pfam: PF24785, PF24786

Enzyme classification (BRENDA):

• EC 2.4.2.61 — alpha-dystroglycan beta1,4-xylosyltransferase (BRENDA: 1 organisms, 3 substrates, 0 inhibitors, 0 Km, 0 kcat entries)

Catalyzed reactions (Rhea), 1 shown:

• 3-O-[Rib-ol-P-Rib-ol-P-3-beta-D-GalNAc-(1->3)-beta-D-GlcNAc-(1->4)-(O-6-P-alpha-D-Man)]-Thr-[protein] + UDP-alpha-D-xylose = 3-O-[beta-D-Xyl-(1->4)-Rib-ol-P-Rib-ol-P-3-beta-D-GalNAc-(1->3)-beta-D-GlcNAc-(1->4)-(O-6-P-alpha-D-Man)]-Thr-[protein] + UDP + H(+) (RHEA:57880)

UniProt features (9 total): sequence variant 3, topological domain 2, chain 1, transmembrane region 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y2B1-F1	85.72	0.72

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9939291	Matriglycan biosynthesis on DAG1

MSigDB gene sets: 230 (showing top): LIANG_HEMATOPOIESIS_STEM_CELL_NUMBER_SMALL_VS_HUGE_UP, PAL_PRMT5_TARGETS_UP, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, BROWNE_HCMV_INFECTION_24HR_UP, MARTINEZ_RB1_TARGETS_DN, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, MODULE_206, JAATINEN_HEMATOPOIETIC_STEM_CELL_UP, RASHI_RESPONSE_TO_IONIZING_RADIATION_5, DANG_BOUND_BY_MYC, MARTINEZ_RB1_AND_TP53_TARGETS_UP, GOBP_PROTEIN_O_LINKED_GLYCOSYLATION, GOBP_GLYCOPROTEIN_METABOLIC_PROCESS, BLALOCK_ALZHEIMERS_DISEASE_DN, BENPORATH_MYC_MAX_TARGETS

GO Biological Process (3): protein O-linked glycosylation (GO:0006493), protein O-linked glycosylation via mannose (GO:0035269), obsolete protein glycosylation (GO:0006486)

GO Molecular Function (3): ribitol beta-1,4-xylosyltransferase activity (GO:0120053), protein binding (GO:0005515), transferase activity (GO:0016740)

GO Cellular Component (5): Golgi membrane (GO:0000139), nucleoplasm (GO:0005654), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), membrane (GO:0016020)

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
glycoprotein biosynthetic process	1
protein O-linked glycosylation	1
UDP-xylosyltransferase activity	1
binding	1
catalytic activity	1
Golgi apparatus	1
bounding membrane of organelle	1
nuclear lumen	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

616 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RXYLT1	FKRP	Q9H9S5	920
RXYLT1	POMGNT2	Q8NAT1	893
RXYLT1	POMK	Q9H5K3	877
RXYLT1	B3GALNT2	Q8NCR0	876
RXYLT1	FKTN	O75072	862
RXYLT1	B4GAT1	O43505	858
RXYLT1	POMT1	Q9Y6A1	858
RXYLT1	POMT2	Q9UKY4	855
RXYLT1	POMGNT1	Q8WZA1	814
RXYLT1	GMPPB	Q9Y5P6	813
RXYLT1	DOLK	Q9UPQ8	769
RXYLT1	DPM2	O94777	762
RXYLT1	LARGE1	O95461	756
RXYLT1	CRPPA	A4D126	752
RXYLT1	DPM3	Q9P2X0	749

IntAct

22 interactions, top by confidence:

A	B	Type	Score
POMGNT1	RXYLT1	psi-mi:“MI:0915”(physical association)	0.740
FKTN	RXYLT1	psi-mi:“MI:0915”(physical association)	0.710
RXYLT1	FKTN	psi-mi:“MI:0915”(physical association)	0.710
RXYLT1	FKTN	psi-mi:“MI:0914”(association)	0.710
RXYLT1	WFS1	psi-mi:“MI:0915”(physical association)	0.560
FKRP	FKTN	psi-mi:“MI:0914”(association)	0.430
FKTN	FKRP	psi-mi:“MI:0914”(association)	0.430
FKRP	FKTN	psi-mi:“MI:0403”(colocalization)	0.430
RXYLT1	STT3B	psi-mi:“MI:0915”(physical association)	0.400
UBE2J1	RXYLT1	psi-mi:“MI:0915”(physical association)	0.400
GPR3	RXYLT1	psi-mi:“MI:0915”(physical association)	0.370
RXYLT1	RTL8C	psi-mi:“MI:0914”(association)	0.350
SAAL1	TMEM223	psi-mi:“MI:0914”(association)	0.350
SLC30A7	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC39A11	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC39A14	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC45A4	EIF3CL	psi-mi:“MI:0914”(association)	0.350
SLC7A1	ESYT2	psi-mi:“MI:0914”(association)	0.350
POMGNT1	RXYLT1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (37): FKTN (Affinity Capture-MS), ATP2B4 (Affinity Capture-MS), ATP2B2 (Affinity Capture-MS), SLC7A3 (Affinity Capture-MS), CLTCL1 (Affinity Capture-MS), CANX (Affinity Capture-MS), POMGNT1 (Affinity Capture-MS), RMND1 (Affinity Capture-MS), FAM127A (Affinity Capture-MS), GALNT12 (Affinity Capture-MS), CHPT1 (Affinity Capture-MS), SEL1L (Affinity Capture-MS), OS9 (Affinity Capture-MS), TMEM5 (Two-hybrid), TMEM5 (Proximity Label-MS)

ESM2 similar proteins: A0A0B5GR44, A7XDQ9, B1WB06, B7ZWR7, B9SLR1, F4HSU3, F4HXW9, F4I6V0, F4KF16, O64884, O81053, P97259, Q08834, Q08CD5, Q09328, Q3E6Y3, Q3U095, Q52KP5, Q5XI89, Q6AX23, Q6NMK1, Q8GUM0, Q8H1E6, Q8L7F9, Q8LPF8, Q8R4G6, Q8RX55, Q8VDX6, Q8VZV7, Q8W486, Q940J9, Q949U4, Q9ASW1, Q9C7F9, Q9CA71, Q9FMW3, Q9FYG0, Q9FZ97, Q9LQ32, Q9LV16

Diamond homologs: Q08CD5, Q8VDX6, Q9Y2B1

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RXYLT1	“form complex”	“Fukutin-FKRP-TMEM5 multienzyme complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	36
Likely pathogenic	11
Uncertain significance	170
Likely benign	193
Benign	12

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1008116	NM_014254.3(RXYLT1):c.994dup (p.Val332fs)	Pathogenic
1380332	NM_014254.3(RXYLT1):c.698G>A (p.Trp233Ter)	Pathogenic
1390275	NM_014254.3(RXYLT1):c.239_240del (p.Arg80fs)	Pathogenic
1502235	NM_014254.3(RXYLT1):c.997G>C (p.Gly333Arg)	Pathogenic
1704385	NM_014254.3(RXYLT1):c.169+2T>C	Pathogenic
2061507	NM_014254.3(RXYLT1):c.360_363del (p.Leu121fs)	Pathogenic
2147254	NM_014254.3(RXYLT1):c.398_402del (p.Gly133fs)	Pathogenic
2166822	NM_014254.3(RXYLT1):c.385C>T (p.Gln129Ter)	Pathogenic
2172075	NM_014254.3(RXYLT1):c.947del (p.Lys316fs)	Pathogenic
2695470	NM_014254.3(RXYLT1):c.476_477insTATT (p.Asn160fs)	Pathogenic
2711005	NM_014254.3(RXYLT1):c.200del (p.Asn67fs)	Pathogenic
2742503	NM_014254.3(RXYLT1):c.725G>A (p.Trp242Ter)	Pathogenic
2772011	NM_014254.3(RXYLT1):c.508dup (p.Glu170fs)	Pathogenic
2781094	NM_014254.3(RXYLT1):c.207G>A (p.Trp69Ter)	Pathogenic
2783807	NM_014254.3(RXYLT1):c.157A>T (p.Arg53Ter)	Pathogenic
2806984	NM_014254.3(RXYLT1):c.515_519del (p.Ala172fs)	Pathogenic
2832051	NM_014254.3(RXYLT1):c.539G>A (p.Trp180Ter)	Pathogenic
2833523	NM_014254.3(RXYLT1):c.482_489del (p.Asn161fs)	Pathogenic
2833922	NM_014254.3(RXYLT1):c.553C>T (p.Gln185Ter)	Pathogenic
2843288	NM_014254.3(RXYLT1):c.613_623del (p.Glu204_His205insTer)	Pathogenic
2853169	NM_014254.3(RXYLT1):c.932del (p.Thr311fs)	Pathogenic
2885748	NM_014254.3(RXYLT1):c.699del (p.Pro232_Trp233insTer)	Pathogenic
2912230	NM_014254.3(RXYLT1):c.119dup (p.Arg41fs)	Pathogenic
2990545	NM_014254.3(RXYLT1):c.501_511del (p.Asn167fs)	Pathogenic
2990579	NM_014254.3(RXYLT1):c.301C>T (p.Gln101Ter)	Pathogenic
3006120	NM_014254.3(RXYLT1):c.896G>A (p.Trp299Ter)	Pathogenic
3244418	NC_000012.11:g.(?64173741)(64174974_?)del	Pathogenic
3696338	NM_014254.3(RXYLT1):c.533_536dup (p.Gln179fs)	Pathogenic
39603	NM_014254.3(RXYLT1):c.795del (p.Arg266fs)	Pathogenic
39607	NM_014254.3(RXYLT1):c.279del (p.Gly94fs)	Pathogenic

SpliceAI

1228 predictions. Top by Δscore:

Variant	Effect	Δscore
12:63781017:A:AG	acceptor_gain	1.0000
12:63781018:G:GG	acceptor_gain	1.0000
12:63781018:GAACA:G	acceptor_gain	1.0000
12:63802406:G:GG	donor_gain	1.0000
12:63805400:GAACA:G	donor_gain	1.0000
12:63805405:G:GG	donor_gain	1.0000
12:63779975:G:GT	donor_gain	0.9900
12:63780092:G:GT	donor_gain	0.9900
12:63781012:A:AG	acceptor_gain	0.9900
12:63781013:A:G	acceptor_gain	0.9900
12:63781014:A:AG	acceptor_gain	0.9900
12:63781016:CA:C	acceptor_loss	0.9900
12:63781017:A:C	acceptor_loss	0.9900
12:63781018:G:GA	acceptor_loss	0.9900
12:63781018:GA:G	acceptor_gain	0.9900
12:63781018:GAA:G	acceptor_gain	0.9900
12:63781018:GAAC:G	acceptor_gain	0.9900
12:63781171:ATTGG:A	donor_loss	0.9900
12:63781172:TTGG:T	donor_loss	0.9900
12:63781175:G:GG	donor_gain	0.9900
12:63781175:GTAA:G	donor_loss	0.9900
12:63781176:T:TG	donor_loss	0.9900
12:63781177:AA:A	donor_loss	0.9900
12:63782539:A:AG	acceptor_gain	0.9900
12:63782540:G:GG	acceptor_gain	0.9900
12:63782700:GACCT:G	donor_gain	0.9900
12:63784969:GGCTT:G	acceptor_gain	0.9900
12:63785043:A:T	donor_gain	0.9900
12:63789860:A:AG	acceptor_gain	0.9900
12:63789861:C:G	acceptor_gain	0.9900

AlphaMissense

2919 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:63802386:T:A	W242R	0.998
12:63802386:T:C	W242R	0.998
12:63802200:T:A	W180R	0.995
12:63802200:T:C	W180R	0.995
12:63805239:G:C	R250T	0.994
12:63808678:G:C	W306C	0.994
12:63808678:G:T	W306C	0.994
12:63808733:A:C	S325R	0.994
12:63808735:T:A	S325R	0.994
12:63808735:T:G	S325R	0.994
12:63808740:T:C	L327P	0.994
12:63805239:G:T	R250M	0.993
12:63805240:G:C	R250S	0.993
12:63805240:G:T	R250S	0.993
12:63802290:T:A	W210R	0.991
12:63802290:T:C	W210R	0.991
12:63808925:T:A	W389R	0.991
12:63808925:T:C	W389R	0.991
12:63802255:T:A	V198D	0.990
12:63805298:T:C	C270R	0.990
12:63808676:T:A	W306R	0.990
12:63808676:T:C	W306R	0.990
12:63802153:T:C	L164P	0.989
12:63802395:G:A	G245R	0.989
12:63802395:G:C	G245R	0.989
12:63808790:G:C	A344P	0.989
12:63784981:T:A	W113R	0.988
12:63784981:T:C	W113R	0.988
12:63805303:T:A	N271K	0.988
12:63805303:T:G	N271K	0.988

dbSNP variants (sampled 300 via entrez): RS1000059402 (12:63779140 G>A), RS1000066773 (12:63808038 G>A,C), RS1000134125 (12:63805465 T>C), RS1000436915 (12:63805127 C>A,G), RS1000647439 (12:63797659 A>G,T), RS1001087652 (12:63792433 A>T), RS1001127295 (12:63806165 G>A,T), RS1001161137 (12:63809908 TAAAAAA>T,TAA,TAAA,TAAAA,TAAAAA,TAAAAAAA,TAAAAAAAA,TAAAAAAAAAA), RS1001336863 (12:63785587 T>A,C), RS1001337964 (12:63803433 T>C), RS1001456565 (12:63793467 GAAAA>G,GAAAAA), RS1001541328 (12:63796402 G>A), RS1001559517 (12:63792853 C>T), RS1001670505 (12:63790417 A>G), RS1001692450 (12:63805994 T>G)

Disease associations

OMIM: gene MIM:605862 | disease phenotypes: MIM:615041, MIM:236670

GenCC curated gene-disease

Disease	Classification	Inheritance
muscle-eye-brain disease	Definitive	Autosomal recessive
muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 10	Definitive	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
muscle-eye-brain disease	Definitive	AR

Mondo (3): muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 10 (MONDO:0014022), muscular dystrophy-dystroglycanopathy, type A (MONDO:0000171), muscle-eye-brain disease (MONDO:0018939)

Orphanet (1): Walker-Warburg syndrome (Orphanet:899)

HPO phenotypes

56 total (30 of 56 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000133	Gonadal dysgenesis
HP:0000175	Cleft palate
HP:0000176	Submucous cleft hard palate
HP:0000193	Bifid uvula
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000411	Protruding ear
HP:0000482	Microcornea
HP:0000501	Glaucoma
HP:0000518	Cataract
HP:0000528	Anophthalmia
HP:0000541	Retinal detachment
HP:0000556	Retinal dystrophy
HP:0000568	Microphthalmia
HP:0000587	Abnormal optic nerve morphology
HP:0000612	Iris coloboma
HP:0000648	Optic atrophy
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001265	Hyporeflexia
HP:0001274	Agenesis of corpus callosum
HP:0001284	Areflexia
HP:0001302	Pachygyria

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST007623_4	Lack of premeditation	6.000000e-07
GCST010566_7	Benign childhood epilepsy with centro-temporal spikes	8.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006946	behavioural disinhibition measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
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

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases methylation, increases expression	3
Particulate Matter	increases abundance, increases expression, decreases expression, affects cotreatment	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	2
Air Pollutants	increases abundance, increases expression, decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
bisphenol F	affects cotreatment, increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
methylselenic acid	decreases expression	1
trichostatin A	increases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
deguelin	increases expression	1
pyrimidifen	increases expression	1
thifluzamide	increases expression	1
pyrachlostrobin	increases expression	1
Sunitinib	increases expression	1
Ethanol	affects cotreatment, decreases expression, increases abundance	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Caffeine	increases phosphorylation	1
Coumestrol	decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Estradiol	affects cotreatment, decreases expression	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1
Indomethacin	affects cotreatment, increases expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1

Cellosaurus cell lines

6 cell lines: 6 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TS96	HAP1 TMEM5 (-) 1	Cancer cell line	Male
CVCL_TS97	HAP1 TMEM5 (-) 2	Cancer cell line	Male
CVCL_TS98	HAP1 TMEM5 (-) 3	Cancer cell line	Male
CVCL_TS99	HAP1 TMEM5 (-) 4	Cancer cell line	Male
CVCL_TT00	HAP1 TMEM5 (-) 5	Cancer cell line	Male
CVCL_TT01	HAP1 TMEM5 (-) 6	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04001595	Not specified	UNKNOWN	Global FKRP Registry