LRIF1

Summary

LRIF1 (ligand dependent nuclear receptor interacting factor 1, HGNC:30299) is a protein-coding gene on chromosome 1p13.3, encoding Ligand-dependent nuclear receptor-interacting factor 1 (Q5T3J3). Together with SMCHD1, involved in chromosome X inactivation in females by promoting the compaction of heterochromatin.

Predicted to enable nuclear retinoic acid receptor binding activity. Involved in dosage compensation by inactivation of X chromosome. Located in centriolar satellite; chromosome, telomeric region; and nuclear lumen. Implicated in facioscapulohumeral muscular dystrophy 3.

Source: NCBI Gene 55791 — RefSeq curated summary.

At a glance

• Gene–disease (curated): facioscapulohumeral muscular dystrophy (Moderate, GenCC) — +1 more curated relationship
• GWAS associations: 7
• Clinical variants (ClinVar): 768 total — 15 pathogenic, 11 likely-pathogenic
• Phenotypes (HPO): 11
• MANE Select transcript: NM_018372

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30299
Approved symbol	LRIF1
Name	ligand dependent nuclear receptor interacting factor 1
Location	1p13.3
Locus type	gene with protein product
Status	Approved
Aliases	RIF1, FLJ11269
Ensembl gene	ENSG00000121931
Ensembl biotype	protein_coding
OMIM	615354
Entrez	55791

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000369763, ENST00000485275, ENST00000494675, ENST00000894506

RefSeq mRNA: 2 — MANE Select: NM_018372 NM_001006945, NM_018372

CCDS: CCDS30800, CCDS41366

Canonical transcript exons

ENST00000369763 — 4 exons

Exon	Start	End
ENSE00001630531	110951288	110952815
ENSE00002158395	110947190	110948399
ENSE00002167719	110963621	110963922
ENSE00003653881	110949851	110950123

Expression profiles

Bgee: expression breadth ubiquitous, 271 present calls, max score 91.42.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.5865 / max 445.3296, expressed in 1815 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
13791	19.0469	1803
13792	8.3238	1761
13789	0.7559	445
13790	0.2852	101
13788	0.1747	63

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	91.42	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.89	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.99	gold quality
choroid plexus epithelium	UBERON:0003911	88.43	gold quality
sperm	CL:0000019	88.18	gold quality
right testis	UBERON:0004534	87.54	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	86.97	gold quality
left testis	UBERON:0004533	86.85	gold quality
testis	UBERON:0000473	86.84	gold quality
male germ cell	CL:0000015	86.77	gold quality
hindlimb stylopod muscle	UBERON:0004252	86.35	gold quality
corpus epididymis	UBERON:0004359	86.28	gold quality
muscle of leg	UBERON:0001383	85.93	gold quality
gastrocnemius	UBERON:0001388	85.92	gold quality
palpebral conjunctiva	UBERON:0001812	84.67	gold quality
adrenal tissue	UBERON:0018303	83.92	gold quality
heart left ventricle	UBERON:0002084	83.68	gold quality
granulocyte	CL:0000094	83.64	gold quality
stromal cell of endometrium	CL:0002255	83.58	gold quality
cortical plate	UBERON:0005343	83.51	gold quality
cardiac ventricle	UBERON:0002082	83.49	gold quality
muscle organ	UBERON:0001630	83.47	gold quality
placenta	UBERON:0001987	83.01	gold quality
right lobe of liver	UBERON:0001114	82.91	gold quality
lymph node	UBERON:0000029	82.46	gold quality
islet of Langerhans	UBERON:0000006	82.17	gold quality
heart	UBERON:0000948	81.61	gold quality
anterior cingulate cortex	UBERON:0009835	81.57	gold quality
cingulate cortex	UBERON:0003027	81.45	gold quality
heart right ventricle	UBERON:0002080	81.36	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.66
E-GEOD-99795	no	116.23

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

48 targeting LRIF1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-181B-2-3P	99.81	70.06	1646
HSA-MIR-181B-3P	99.81	70.06	1646
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-10393-5P	99.65	68.01	1368
HSA-MIR-4502	99.65	66.99	1021
HSA-MIR-5004-3P	99.54	68.27	1371
HSA-MIR-409-3P	99.50	66.33	1192
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-155-5P	99.35	70.16	1509
HSA-MIR-6882-5P	99.35	71.13	1206
HSA-MIR-4311	99.31	70.47	3041
HSA-MIR-3692-5P	99.29	67.04	1421
HSA-MIR-6734-3P	99.15	66.27	1627

Literature-anchored findings (GeneRIF, showing 4)

• RIF1 is a novel nuclear matrix transcription repressor: a potential role of RIF1 regulation of nuclear receptor transcriptional activity. (PMID:17455211)
• Thus, the molecular network involving HBiX1 (previously termed C1orf103) and SMCHD1 links the H3K9me3 and XIST-H3K27me3 domains to organize the compact inactive X chromosome structure. (PMID:23542155)
• LRIF1 interacts directly with HP1 alpha chromoshadow domain via an evolutionarily conserved PXVXL motif within its C-terminus. Importantly, the LRIF1-HP1 alpha interaction is critical for Aurora B activity in the inner centromere. (PMID:30016453)
• SMCHD1 and LRIF1 converge at the FSHD-associated D4Z4 repeat and LRIF1 promoter yet display different modes of action. (PMID:37380887)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	lrif1	ENSDARG00000069696
mus_musculus	Lrif1	ENSMUSG00000056260
rattus_norvegicus	Lrif1	ENSRNOG00000017784

Protein

Protein identifiers

Ligand-dependent nuclear receptor-interacting factor 1 — Q5T3J3 (reviewed: Q5T3J3)

Alternative names: HP1-binding protein enriched in inactive X chromosome protein 1, Receptor-interacting factor 1

All UniProt accessions (1): Q5T3J3

UniProt curated annotations — full annotation on UniProt →

Function. Together with SMCHD1, involved in chromosome X inactivation in females by promoting the compaction of heterochromatin. Also able to repress the ligand-induced transcriptional activity of retinoic acid receptor alpha (RARA), possibly through direct recruitment of histone deacetylases. Also required for silencing of the DUX4 locus in somatic cells.

Subunit / interactions. Interacts with RARA. Interacts with SMCHD1; leading to recruitment to inactivated chromosome X in females. Interacts (via PxVxL motif) with HP1 (CBX1/HP1-beta, CBX3/HP1-gamma and CBX5/HP1-alpha).

Subcellular location. Chromosome. Nucleus matrix.

Tissue specificity. Widely expressed, with the highest expression levels in heart, liver and placenta.

Disease relevance. Facioscapulohumeral muscular dystrophy 3, digenic (FSHD3) [MIM:619477] A form of facioscapulohumeral muscular dystrophy, a degenerative muscle disease characterized by slowly progressive weakness of the muscles of the face, upper-arm, and shoulder girdle. FSHD3 is a digenic form characterized by adult onset of proximal muscle weakness affecting the face, neck, scapular muscles, and upper and lower limbs. Muscle involvement is usually asymmetric, and other muscle groups may become involved with progression of the disease. The disease is caused by variants affecting distinct genetic loci, including the gene represented in this entry. The disease is caused by a LRIF1 homozygous variant resulting in loss of isoform 1, in the presence of a haplotype on chromosome 4 permissive for chromatin relaxation of the D4Z4 macrosatellite and inappropriate DUX4 expression. Deregulated expression of DUX4 in skeletal muscle can lead to cell death.

Domain organisation. The Pro-Xaa-Val-Xaa-Leu (PxVxL) motif mediates interaction with HP1 (CBX1/HP1-beta, CBX3/HP1-gamma and CBX5/HP1-alpha).

Similarity. Belongs to the LRIF1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5T3J3-1	1	yes
Q5T3J3-2	2

RefSeq proteins (2): NP_001006946, NP_060842* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026191	LRIF1	Family

Pfam: PF15741

UniProt features (30 total): modified residue 6, cross-link 5, sequence conflict 4, sequence variant 3, mutagenesis site 3, short sequence motif 3, region of interest 2, chain 1, splice variant 1, coiled-coil region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5T3J3-F1	48.88	0.04

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 (11): 436, 502, 599, 732, 259, 279, 446, 605, 702, 402, 430

Mutagenesis-validated functional residues (3):

Position	Phenotype
582–584	abolishes interaction with hp1 (cbx1/hp1-beta, cbx3/hp1-gamma and cbx5/hp1-alpha).
628–630	slightly reduces nuclear localization.
642–644	abolishes nuclear localization.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 140 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, DARWICHE_SKIN_TUMOR_PROMOTER_UP, DARWICHE_PAPILLOMA_RISK_LOW_UP, DARWICHE_PAPILLOMA_RISK_HIGH_UP, DARWICHE_SQUAMOUS_CELL_CARCINOMA_DN, YORDY_RECIPROCAL_REGULATION_BY_ETS1_AND_SP100_DN, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, MUELLER_PLURINET, GOBP_CHROMATIN_REMODELING, GOBP_HETEROCHROMATIN_ORGANIZATION, GOBP_EPIGENETIC_REGULATION_OF_GENE_EXPRESSION, GOCC_CHROMOSOMAL_REGION, GOCC_SEX_CHROMOSOME, MARSON_BOUND_BY_FOXP3_STIMULATED

GO Biological Process (2): regulation of DNA-templated transcription (GO:0006355), dosage compensation by inactivation of X chromosome (GO:0009048)

GO Molecular Function (2): nuclear retinoic acid receptor binding (GO:0042974), protein binding (GO:0005515)

GO Cellular Component (7): Barr body (GO:0001740), nucleoplasm (GO:0005654), nuclear matrix (GO:0016363), centriolar satellite (GO:0034451), chromosome, telomeric region (GO:0000781), nucleus (GO:0005634), chromosome (GO:0005694)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
nuclear lumen	2
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
sex-chromosome dosage compensation	1
heterochromatin formation	1
nuclear receptor binding	1
binding	1
nuclear chromosome	1
X chromosome	1
condensed chromatin of inactivated sex chromosome	1
centrosome	1
chromosomal region	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

774 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LRIF1	SMCHD1	A6NHR9	943
LRIF1	DUX4L2	P0CJ85	622
LRIF1	TRAK2	O60296	527
LRIF1	ZNF512	Q96ME7	469
LRIF1	RRP15	Q9Y3B9	468
LRIF1	SDAD1	Q9NVU7	455
LRIF1	RANBP10	Q6VN20	429
LRIF1	RMND5A	Q9H871	426
LRIF1	HERC2	O95714	421
LRIF1	DNMT3B	Q9UBC3	418
LRIF1	TRIM43	Q96BQ3	417
LRIF1	KIF5C	O60282	410
LRIF1	SRBD1	Q8N5C6	406
LRIF1	MBD3L2	Q8NHZ7	401
LRIF1	CACYBP	Q9HB71	397

IntAct

225 interactions, top by confidence:

A	B	Type	Score
PSMC3	PSMD9	psi-mi:“MI:0914”(association)	0.940
CBX3	LRIF1	psi-mi:“MI:0915”(physical association)	0.880
CBX5	LRIF1	psi-mi:“MI:0915”(physical association)	0.870
LRIF1	CBX5	psi-mi:“MI:0915”(physical association)	0.870
LRIF1	SMCHD1	psi-mi:“MI:0914”(association)	0.680
LRIF1	SMCHD1	psi-mi:“MI:0915”(physical association)	0.680
GADD45G	LRIF1	psi-mi:“MI:0915”(physical association)	0.670
CBX3	E2F6	psi-mi:“MI:0914”(association)	0.640
PSMC3	PSMD12	psi-mi:“MI:0914”(association)	0.640
POLR2F	POLR3A	psi-mi:“MI:0914”(association)	0.640
VPS26C	LRIF1	psi-mi:“MI:0915”(physical association)	0.560
CRACR2A	LRIF1	psi-mi:“MI:0915”(physical association)	0.560
SPATA18	LRIF1	psi-mi:“MI:0915”(physical association)	0.560
PRKAB2	LRIF1	psi-mi:“MI:0915”(physical association)	0.560
UNC119	LRIF1	psi-mi:“MI:0915”(physical association)	0.560
POLR1C	LRIF1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (296): LRIF1 (Protein-peptide), LRIF1 (Affinity Capture-MS), LRIF1 (Affinity Capture-MS), LRIF1 (Affinity Capture-MS), LRIF1 (Affinity Capture-MS), LRIF1 (Affinity Capture-MS), LRIF1 (Affinity Capture-MS), LRIF1 (Two-hybrid), LRIF1 (Proximity Label-MS), LRIF1 (Proximity Label-MS), LRIF1 (Proximity Label-MS), MVD (Affinity Capture-MS), PPM1G (Affinity Capture-MS), CHAF1B (Affinity Capture-MS), DCTN3 (Affinity Capture-MS)

ESM2 similar proteins: A0JNH1, A2RRX6, A6QNQ6, B2RRE4, B2RRF6, D3Z987, O75362, P56716, Q01954, Q0VBV7, Q28BT7, Q2M2Z5, Q32N19, Q3TNU4, Q3U0P1, Q3URK3, Q3UXL4, Q3V089, Q3V0A6, Q499M7, Q499R0, Q5DTT3, Q5HZI1, Q5R9I1, Q5RC05, Q5T3J3, Q5VWN6, Q6AHZ1, Q6NU19, Q6PG16, Q7TSH4, Q7Z4V0, Q86XD8, Q86YC2, Q8CDD9, Q8IXJ9, Q8MJ03, Q8MJ04, Q8MJ05, Q8NAP3

Diamond homologs: Q499M7, Q5T3J3, Q8CDD9

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
UHRF1	“down-regulates activity”	LRIF1	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 164 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
Cytosolic sensors of pathogen-associated DNA	5	13.7×	3e-03
mRNA Splicing - Minor Pathway	5	10.8×	5e-03
Nonhomologous End-Joining (NHEJ)	6	9.7×	3e-03
Regulation of RAS by GAPs	5	9.3×	7e-03
ChAHP complex assembly	5	8.9×	7e-03
mRNA Splicing	8	8.4×	6e-04
mRNA Polyadenylation	9	7.6×	6e-04
Regulation of endogenous retroelements by KRAB-ZFP proteins	7	7.2×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	15
Likely pathogenic	11
Uncertain significance	480
Likely benign	145
Benign	11

Top pathogenic / likely-pathogenic (26)

Variant ID	HGVS	Classification
1047890	GRCh37/hg19 2q21.3-23.3(chr2:136473383-152727396)	Pathogenic
1202610	NM_018372.4(LRIF1):c.869_872dup (p.Trp291Ter)	Pathogenic
1427957	NM_001164508.2(NEB):c.22966del (p.Val7656fs)	Pathogenic
1451650	NM_001164508.2(NEB):c.24376_24377insCC (p.Gln8126fs)	Pathogenic
1453846	NM_001164508.2(NEB):c.22175del (p.Lys7392fs)	Pathogenic
2023151	NM_001164508.2(NEB):c.24510dup (p.Lys8171fs)	Pathogenic
2030542	NM_001164508.2(NEB):c.22931del (p.Glu7644fs)	Pathogenic
2042915	NM_001164508.2(NEB):c.24469C>T (p.Gln8157Ter)	Pathogenic
212737	NM_001164508.2(NEB):c.24477_24480dup (p.Ser8161delinsTyrTer)	Pathogenic
2817523	NM_001164508.2(NEB):c.24683_24684del (p.Lys8228fs)	Pathogenic
432817	NM_001164508.2(NEB):c.24588C>G (p.Tyr8196Ter)	Pathogenic
506284	NM_001164508.2(NEB):c.22144A>C (p.Thr7382Pro)	Pathogenic
859754	NM_001164508.2(NEB):c.22312_22315dup (p.Thr7439fs)	Pathogenic
918157	NM_001164508.2(NEB):c.22831C>T (p.Arg7611Ter)	Pathogenic
968758	NM_001164508.2(NEB):c.22645G>T (p.Glu7549Ter)	Pathogenic
1526921	GRCh37/hg19 2q23.3(chr2:150606201-153038451)	Likely pathogenic
1724747	NM_001164508.2(NEB):c.22315dup (p.Thr7439fs)	Likely pathogenic
1724779	NM_001164508.2(NEB):c.22294_22295insCAGATTTA (p.Lys7432fs)	Likely pathogenic
1725467	NM_001164508.2(NEB):c.22804A>T (p.Lys7602Ter)	Likely pathogenic
1994238	NM_001164508.2(NEB):c.24301-1G>T	Likely pathogenic
3584397	NM_001164508.2(NEB):c.25201dup (p.Ser8401fs)	Likely pathogenic
3776963	NM_001164508.2(NEB):c.22924del (p.Tyr7642fs)	Likely pathogenic
4814762	NM_001164508.2(NEB):c.23668del (p.Ala7889_Ile7890insTer)	Likely pathogenic
4814765	NM_001164508.2(NEB):c.24276dup (p.His8093fs)	Likely pathogenic
554692	NM_001164508.2(NEB):c.23929-2A>C	Likely pathogenic
558061	NM_001164508.2(NEB):c.23834C>A (p.Ser7945Ter)	Likely pathogenic

SpliceAI

766 predictions. Top by Δscore:

Variant	Effect	Δscore
1:110948395:TTCTG:T	acceptor_gain	1.0000
1:110948408:T:C	acceptor_gain	1.0000
1:110948408:T:TC	acceptor_gain	1.0000
1:110948417:A:C	acceptor_gain	1.0000
1:110948421:C:CT	acceptor_gain	1.0000
1:110948421:C:T	acceptor_gain	1.0000
1:110950052:T:TA	donor_gain	1.0000
1:110950119:TGGAT:T	acceptor_gain	1.0000
1:110950120:GGAT:G	acceptor_gain	1.0000
1:110950121:GAT:G	acceptor_gain	1.0000
1:110950122:AT:A	acceptor_gain	1.0000
1:110950124:C:CC	acceptor_gain	1.0000
1:110950129:A:AC	acceptor_gain	1.0000
1:110950130:T:C	acceptor_gain	1.0000
1:110950130:T:TC	acceptor_gain	1.0000
1:110948397:CTG:C	acceptor_gain	0.9900
1:110948398:TG:T	acceptor_gain	0.9900
1:110948403:CAA:C	acceptor_gain	0.9900
1:110948405:A:AC	acceptor_gain	0.9900
1:110948405:A:C	acceptor_gain	0.9900
1:110948407:A:C	acceptor_gain	0.9900
1:110948416:C:CT	acceptor_gain	0.9900
1:110948422:A:T	acceptor_gain	0.9900
1:110949847:CTAC:C	donor_loss	0.9900
1:110949850:C:CG	donor_loss	0.9900
1:110950129:A:C	acceptor_gain	0.9900
1:110948399:GC:G	acceptor_loss	0.9800
1:110948400:C:CC	acceptor_gain	0.9800
1:110948400:C:T	acceptor_loss	0.9800
1:110948401:T:A	acceptor_loss	0.9800

AlphaMissense

5055 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:110952324:A:G	I187T	0.996
1:110951811:A:T	V358D	0.995
1:110948000:C:G	A757P	0.994
1:110948026:A:G	L748P	0.994
1:110952750:A:G	L45S	0.993
1:110952198:A:T	V229D	0.992
1:110951814:A:G	L357S	0.991
1:110947981:C:G	R763P	0.989
1:110947997:C:G	A758P	0.989
1:110952282:A:G	L201S	0.989
1:110952313:C:G	A191P	0.989
1:110952324:A:C	I187S	0.989
1:110952189:A:T	V232E	0.988
1:110952312:G:T	A191D	0.988
1:110948014:A:G	L752P	0.987
1:110948022:C:A	K749N	0.985
1:110948022:C:G	K749N	0.985
1:110952330:A:G	L185S	0.985
1:110948005:T:A	K755I	0.983
1:110947993:A:G	L759P	0.982
1:110951791:A:C	Y365D	0.982
1:110952013:A:G	W291R	0.981
1:110952013:A:T	W291R	0.981
1:110948026:A:T	L748H	0.979
1:110951818:C:G	A356P	0.979
1:110952799:A:C	Y29D	0.979
1:110952180:A:T	V235E	0.977
1:110952258:A:T	I209K	0.977
1:110948035:A:G	I745T	0.976
1:110952324:A:T	I187N	0.975

dbSNP variants (sampled 300 via entrez): RS1000001229 (1:110944713 A>C), RS1000028461 (1:110933323 T>C), RS1000044035 (1:110943622 G>A), RS1000097644 (1:110908889 C>A,T), RS1000132727 (1:110927021 T>C,G), RS1000168117 (1:110907485 C>T), RS1000245209 (1:110946337 G>C), RS1000275003 (1:110889414 C>G), RS1000281431 (1:110895876 C>T), RS1000289726 (1:110896238 T>A), RS1000331756 (1:110927571 G>C), RS1000388577 (1:110932748 T>C), RS1000398675 (1:110903244 G>C), RS1000457835 (1:110909788 T>C), RS1000575800 (1:110883176 T>C)

Disease associations

OMIM: gene MIM:615354 | disease phenotypes: MIM:256030, MIM:619334, MIM:619477

GenCC curated gene-disease

Disease	Classification	Inheritance
facioscapulohumeral muscular dystrophy	Moderate	Autosomal recessive
facioscapulohumeral muscular dystrophy 3, digenic	Limited	Unknown

Mondo (7): nemaline myopathy 2 (MONDO:0009725), strabismus (MONDO:0003432), arthrogryposis multiplex congenita 6 (MONDO:0030281), facioscapulohumeral muscular dystrophy 3, digenic (MONDO:0030354), nebulin-related early-onset distal myopathy (MONDO:0018371), nemaline myopathy (MONDO:0018958), facioscapulohumeral muscular dystrophy (MONDO:0001347)

Orphanet (2): Autosomal recessive distal nebulin myopathy (Orphanet:399103), Nemaline myopathy (Orphanet:607)

HPO phenotypes

11 total (11 of 11 shown, HPO-id order):

HPO	Term
HP:0000467	Neck muscle weakness
HP:0003547	Shoulder girdle muscle weakness
HP:0003551	Difficulty climbing stairs
HP:0003596	Middle age onset
HP:0003691	Scapular winging
HP:0003701	Proximal muscle weakness
HP:0010984	Digenic inheritance
HP:0011951	Aspiration pneumonia
HP:0012378	Fatigue
HP:0030319	Weakness of facial musculature
HP:0034045	Angulated muscle fibers

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST001740_4	Lung cancer	5.000000e-06
GCST007998_7	Intraocular pressure	1.000000e-08
GCST009378_5	Bone mineral content	2.000000e-07
GCST009391_758	Metabolite levels	6.000000e-06
GCST90002390_378	Mean corpuscular hemoglobin	2.000000e-13
GCST90002392_219	Mean corpuscular volume	6.000000e-16
GCST90002397_818	Mean spheric corpuscular volume	6.000000e-18

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004695	intraocular pressure measurement
EFO:0007621	bone mineral content measurement
EFO:0010391	sphingomyelin 16:0 measurement
EFO:0004527	mean corpuscular hemoglobin

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D020391	Muscular Dystrophy, Facioscapulohumeral	C05.651.534.500.400; C10.668.491.175.500.400; C16.320.577.400
D017696	Myopathies, Nemaline	C05.651.575.290; C10.668.491.550.290
D013285	Strabismus	C10.292.562.887; C11.590.810
C538349	Nemaline Myopathy 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, affects expression, decreases expression, affects cotreatment, increases abundance	4
Air Pollutants	decreases expression, increases abundance, increases expression	3
Air Pollutants, Occupational	affects expression, decreases expression	2
Benzo(a)pyrene	decreases expression, affects methylation	2
Smoke	increases abundance, decreases expression	2
Tobacco Smoke Pollution	increases expression	2
Valproic Acid	affects expression, decreases methylation, increases expression	2
Cadmium Chloride	increases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
TAK-243	increases sumoylation	1
bisphenol A	affects methylation	1
2-methyl-4-isothiazolin-3-one	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
cadmium sulfate	increases expression	1
di-n-butylphosphoric acid	affects expression	1
K 7174	increases expression	1
abrine	increases expression	1
jinfukang	decreases expression	1
PCI 5002	affects cotreatment, increases expression	1
Acetaminophen	increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Caffeine	affects phosphorylation	1
Coal	decreases expression, increases abundance	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Hydrogen Peroxide	affects expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Methyl Methanesulfonate	increases expression	1

Cellosaurus cell lines

6 cell lines: 6 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_EE36	RCi006-A	Induced pluripotent stem cell	Male
CVCL_EE37	RCi009-A	Induced pluripotent stem cell	Female
CVCL_II96	RCi005-A	Induced pluripotent stem cell	Female
CVCL_II97	RCi007-C	Induced pluripotent stem cell	Female
CVCL_RF95	RCi007-A	Induced pluripotent stem cell	Female
CVCL_WU25	RCi007-B	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00461656	PHASE4	COMPLETED	Povidone-iodine Antisepsis for Strabismus Surgery
NCT01901588	PHASE4	COMPLETED	Efficacy of Single-Shot Dexmedetomidine Versus Placebo in Preventing Pediatric Emergence Delirium in Strabismus Surgery
NCT02379546	PHASE4	COMPLETED	The Effect of Anaesthesia Depth on Oculo-cardiac Reflex
NCT03349515	PHASE4	COMPLETED	The Effect of Povidone-iodine Ophthalmic Surgical Prep Solution on Respiration in Children Undergoing Strabismus Surgery With General Anesthesia.
NCT04549844	PHASE4	UNKNOWN	Peribulbar Block for Prevention of Oculocardiac Reflex
NCT06035757	PHASE4	RECRUITING	The Occurrence of Emergence Agitation in Pediatric Strabismus Surgery
NCT06560268	PHASE4	NOT_YET_RECRUITING	Low Flow Anesthesia in Children Undergoing Strabismus Surgery
NCT05397470	PHASE3	TERMINATED	Efficacy and Safety of Losmapimod in Treating Participants With Facioscapulohumeral Muscular Dystrophy (FSHD) (REACH)
NCT07038200	PHASE3	RECRUITING	A Study to Evaluate Del-brax (Also Referred to as AOC 1020) in Participants With FSHD
NCT00000128	PHASE3	UNKNOWN	A Trial of Bifocals in Myopic Children With Esophoria
NCT00001864	PHASE3	COMPLETED	Amblyopia (Lazy Eye) Treatment Study
NCT00038753	PHASE3	UNKNOWN	Vision In Preschoolers Study (VIP Study)
NCT01584843	PHASE3	COMPLETED	Efficacy and Safety of GSK1358820 (Botulinum Toxin Type A) in Patients With Strabismus
NCT04060771	PHASE3	UNKNOWN	Post-Operative Nausea and Vomiting in Children Submitted to Strabismus Surgery
NCT06863675	PHASE3	NOT_YET_RECRUITING	Highly Aspherical Lenslet (HAL) and Binocular Vision (BV) Disorders [HALT X(T) Study]
NCT02927080	PHASE2	TERMINATED	Study of ACE-083 in Patients With Facioscapulohumeral Muscular Dystrophy (FSHD)
NCT03943290	PHASE2	TERMINATED	Extension Study to Evaluate the Long-Term Effects of ACE-083 in Patients With Facioscapulohumeral Muscular Dystrophy (FSHD) and Charcot-Marie Tooth (CMT) Disease Types 1 and X (CMT1 and CMTX)
NCT04003974	PHASE2	COMPLETED	Efficacy and Safety of Losmapimod in Subjects With Facioscapulohumeral Muscular Dystrophy (FSHD)
NCT04264442	PHASE2	TERMINATED	Efficacy and Safety of Losmapimod in Treating Subjects With Facioscapulohumeral Muscular Dystrophy (FSHD) With Open-Label Extension (OLE)
NCT05548556	PHASE2	ACTIVE_NOT_RECRUITING	A Study to Evaluate RO7204239 in Participants With Facioscapulohumeral Muscular Dystrophy
NCT06547216	PHASE2	ACTIVE_NOT_RECRUITING	Phase 2 Open-label Extension Study of AOC 1020 in Participants With Facioscapulohumeral Muscular Dystrophy (FSHD)
NCT07435129	PHASE2	NOT_YET_RECRUITING	Phase 2 Study Evaluating Apitegromab for the Treatment of FSHD
NCT00478907	PHASE2	COMPLETED	Prevention of Complications of Eye Surgery
NCT06689943	PHASE2	NOT_YET_RECRUITING	Pain After Strabismus Surgery
NCT02035501	PHASE2	UNKNOWN	Treatment of TNNT1-Myopathy With L-Tyrosine.
NCT03123913	PHASE1	COMPLETED	Study of Testosterone and rHGH in FSHD
NCT00917982	PHASE1	UNKNOWN	The Effect of Vision Therapy/Orthoptic on Motor & Sensory Status of the 3 to 7 Years Old Strabismic Patients
NCT02246556	PHASE1	TERMINATED	Dichoptic Virtual Reality Therapy for Amblyopia in Adults
NCT00104078	PHASE1/PHASE2	COMPLETED	Study Evaluating MYO-029 in Adult Muscular Dystrophy
NCT02239224	PHASE1/PHASE2	COMPLETED	Safety, Tolerability, Pharmacokinetics, and Biological Activity of ATYR1940 in Adult Participants With Muscular Dystrophy
NCT02531217	PHASE1/PHASE2	COMPLETED	Safety, Tolerability, Pharmacokinetics (PK), and Activity of ATYR1940 in Participants With Muscular Dystrophy - Study Extension
NCT02579239	PHASE1/PHASE2	COMPLETED	Evaluate Safety and Biological Activity of ATYR1940 in Participants With Limb Girdle Muscular Dystrophy 2B (LGMD2B) and Facioscapulohumeral Muscular Dystrophy (FSHD)
NCT02603562	PHASE1/PHASE2	COMPLETED	Evaluate Safety and Biological Activity of ATYR1940 in Participants With Early Onset Facioscapulohumeral Muscular Dystrophy
NCT02836418	PHASE1/PHASE2	COMPLETED	Study to Evaluate the Long-Term Safety, Tolerability, and Biological Activity of ATYR1940 in Participants With Limb Girdle and Facioscapulohumeral Muscular Dystrophy (FSHD)
NCT05747924	PHASE1/PHASE2	COMPLETED	Phase 1/2 Study of AOC 1020 in Participants With Facioscapulohumeral Muscular Dystrophy (FSHD)
NCT06907875	PHASE1/PHASE2	RECRUITING	A First-in-human Study of EPI-321 in Facioscapulohumeral Muscular Dystrophy
NCT00082108	Not specified	RECRUITING	Myotonic Dystrophy and Facioscapulohumeral Muscular Dystrophy Registry
NCT00821548	Not specified	COMPLETED	Electrostimulation of Shoulder Girdle and Quadriceps Muscles in Facioscapulohumeral Muscular Dystrophy Patients
NCT01437345	Not specified	COMPLETED	A Multicenter Collaborative Study on the Clinical Features, Expression Profiling, and Quality of Life of Infantile Onset FSHD
NCT01596803	Not specified	COMPLETED	Effects Antioxidants Supplementation on Muscular Function Patients Facioscapulohumeral Dystrophy (FSHD)