Bell's palsy

Summary

Bell’s palsy (MONDO:0005665) is a disease with 27 cohort genes (64 GWAS associations across 7 studies) and 26 clinical trials. Top therapeutic interventions include apraclonidine, prednisolone, and thiamine ion.

At a glance

• Cohort genes: 27
• GWAS associations: 64
• ClinVar variants: 1
• Clinical trials: 26

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Bell’s palsy
Mondo ID	MONDO:0005665
EFO	EFO:0007167
MeSH	D020330
Orphanet	2810
DOID	DOID:12506
ICD-10-CM	G51.0
NCIT	C26769
SNOMED CT	193093009
UMLS	C0376175
MedGen	87660
Anatomy (UBERON)	UBERON:0001647
Is cancer (heuristic)	no

Also known as: facial nerve palsy · facial nerve paralysis · nerve paralysis, Facial · palsy of facial nerve · paralysis Of Facial nerve

Data availability: 1 ClinVar variant · 64 GWAS associations (7 studies).

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › palsy › facial paralysis › Bell’s palsy

Related subtypes (1): exophthalmic ophthalmoplegia

Subtypes (1): geniculate herpes zoster

Genetics & variants

GWAS landscape

64 GWAS associations across 7 studies. Top hits map to 28 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs9357446	7e-23	CDC5L - SUPT3H	A	1.23
rs56046298	2e-08	ZGPAT	?	0.86
rs531105783	1e-07	MORN4	A	0.06
rs540146895	3e-07	TAF4B	G	4.12
rs9556908	3e-07	FARP1	A	1.13
rs150816383	4e-07	CDH12 - Y_RNA	?	1.18
rs13308728	5e-07	ITGB8 - EEF1A1P27	G	0.89
rs2045340	8e-07	LINC01794 - HNRNPA1P57	T	1.11
rs1394798	8e-07	ERBB4	G	0.9
rs8067216	9e-07	CDK5RAP3 - COPZ2	A	1.12
rs949081	9e-07	TENM4 - RNU6-544P	G	0.9
rs2842765	1e-06	RPS3AP23 - NMBR	A	1.12
rs553911686	1e-06	EYA1	A	3.17
rs61811931	2e-06	EFNA3 - Y_RNA	C	0.64
rs193226531	2e-06	KCNMA1	C	2.12
rs145480862	2e-06	DISC1	T	3.19
rs757708187	2e-06	CDH12 - Y_RNA	C	1.17
rs150521225	2e-06	OSMR-DT	C	3.14
rs338767	2e-06	RPL29P29 - LINC00433	A	1.16
rs146881812	2e-06	RARB	G	4.94
rs6789770	2e-06	ROBO2	G	1.14
rs71673709	2e-06	GRIK2 - R3HDM2P2	TATA	2.33
rs139213873	3e-06	TYRO3 - MGA	T	5.27
rs113034576	3e-06	SLC41A3	G	1.31
rs116113578	3e-06	DNAH8	A	4.13
rs748889443	3e-06	GAPDHP31 - NIFKP3	G	5.41
rs147389517	3e-06	PATJ	C	1.58
rs73206415	4e-06	MAGED4 - MIR8088	T	1.29
rs186783239	4e-06	RN7SL223P - CEP295	C	0.63
rs80136426	4e-06	ATP6V1E1P1 - SLC2A1	T	5.13

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST011354	Skuladottir AT	2021	4,714	1,011,520	A meta-analysis uncovers the first sequence variant conferring risk of Bell’s palsy.
GCST90018843	Sakaue S	2021	1,894	461,346	A cross-population atlas of genetic associations for 220 human phenotypes.
GCST90079838	Backman JD	2021	878	387,048	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90083824	Backman JD	2021	878	387,048	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90018623	Sakaue S	2021	343	178,191	A cross-population atlas of genetic associations for 220 human phenotypes.
GCST90013876	Mbatchou J	2021	0	0	Computationally efficient whole-genome regression for quantitative and binary traits.
GCST90013926	Mbatchou J	2021	0	0	Computationally efficient whole-genome regression for quantitative and binary traits.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	1
Tier 3: regulatory	0
Tier 4: intronic/intergenic	49

MAF distribution

Bucket	Variants
common (>=0.05)	23
low_freq (0.01-0.05)	8
rare (<0.01)	11
unknown	8

Functional consequences

Consequence	Count
intron_variant	31
intergenic_variant	15
non_coding_transcript_exon_variant	2
5_prime_UTR_variant	1
synonymous_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs9357446	6	44479861	G>A,C,T	0.469	intergenic_variant	CDC5L - SUPT3H	7e-23	Tier 4: intronic/intergenic
rs56046298	20	63732289	CGTGTGTGTGT>C,CGTGT,CGTGTGT,CGTGTGTGT,CGTGTGTGTGTGT	0.325	intron_variant	ZGPAT	2e-08	Tier 4: intronic/intergenic
rs531105783	10	97618304	G>A,C	0.004	intron_variant	MORN4	1e-07	Tier 4: intronic/intergenic
rs540146895	18	26389511	C>G		intron_variant	TAF4B	3e-07	Tier 4: intronic/intergenic
rs9556908	13	98210841	A>G	0.292	intron_variant	FARP1	3e-07	Tier 4: intronic/intergenic
rs150816383	5	23007756	CATT>C,CATTATT,CATTATTATT	0.146	intergenic_variant	CDH12 - Y_RNA	4e-07	Tier 4: intronic/intergenic
rs13308728	7	20548564	A>G	0.331	intergenic_variant	ITGB8 - EEF1A1P27	5e-07	Tier 4: intronic/intergenic
rs2045340	2	40815504	T>A,G	0.34	intron_variant	LINC01794 - HNRNPA1P57	8e-07	Tier 4: intronic/intergenic
rs1394798	2	212365917	G>A,C	0.453	intron_variant	ERBB4	8e-07	Tier 4: intronic/intergenic
rs8067216	17	48010831	G>A	0.288	intron_variant	CDK5RAP3 - COPZ2	9e-07	Tier 4: intronic/intergenic
rs949081	11	79600399	A>C,G,T	0.427	intergenic_variant	TENM4 - RNU6-544P	9e-07	Tier 4: intronic/intergenic
rs2842765	6	141946667	G>A	0.248	intron_variant	RPS3AP23 - NMBR	1e-06	Tier 4: intronic/intergenic
rs553911686	8	71306545	G>A		intron_variant	EYA1	1e-06	Tier 4: intronic/intergenic
rs61811931	1	155118700	T>C	0.021	intergenic_variant	EFNA3 - Y_RNA	2e-06	Tier 4: intronic/intergenic
rs193226531	10	77284838	G>C	0.003	intron_variant	KCNMA1	2e-06	Tier 4: intronic/intergenic
rs145480862	1	231964137	A>T	0.002	intron_variant	DISC1	2e-06	Tier 4: intronic/intergenic
rs757708187	5	22937070	CTTTTTTT>C,CT,CTT,CTTT,CTTTT,CTTTTT,CTTTTTT,CTTTTTTTT,CTTTTTTTTT,CTTTTTTTTTT,CTTTTTTTTTTT,CTTTTTTTTTTTTTT,CTTTTTTTTTTTTTTTTTTTT	0.168	intergenic_variant	CDH12 - Y_RNA	2e-06	Tier 4: intronic/intergenic
rs150521225	5	38683196	T>C	0.001	non_coding_transcript_exon_variant	OSMR-DT	2e-06	Tier 4: intronic/intergenic
rs338767	13	88476184	A>C,G,T	0.118	non_coding_transcript_exon_variant	RPL29P29 - LINC00433	2e-06	Tier 4: intronic/intergenic
rs146881812	3	25329481	A>G	0.002	intron_variant	RARB	2e-06	Tier 4: intronic/intergenic
rs6789770	3	76331706	C>A,G,T	0.149	intron_variant	ROBO2	2e-06	Tier 4: intronic/intergenic
rs71673709	6	103880871	T>TATA	0.014	intergenic_variant	GRIK2 - R3HDM2P2	2e-06	Tier 4: intronic/intergenic
rs139213873	15	41618286	C>T		intron_variant	TYRO3 - MGA	3e-06	Tier 4: intronic/intergenic
rs113034576	3	126069922	A>G	0.031	intron_variant	SLC41A3	3e-06	Tier 4: intronic/intergenic
rs116113578	6	38870209	G>A,C		intron_variant	DNAH8	3e-06	Tier 4: intronic/intergenic
rs748889443	12	7581101	A>G		intergenic_variant	GAPDHP31 - NIFKP3	3e-06	Tier 4: intronic/intergenic
rs147389517	1	62151581	A>C	0.012	intron_variant	PATJ	3e-06	Tier 4: intronic/intergenic
rs73206415	X	52221384	C>T	0.019	intron_variant	MAGED4 - MIR8088	4e-06	Tier 4: intronic/intergenic
rs186783239	11	93639286	T>C	0.011	intergenic_variant	RN7SL223P - CEP295	4e-06	Tier 4: intronic/intergenic
rs80136426	1	42907291	C>T	0.002	intron_variant	ATP6V1E1P1 - SLC2A1	4e-06	Tier 4: intronic/intergenic

ClinVar germline variants

1 retrieved; paginated sample, class counts are floors:

1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
267932	46;XX;t(1;13)(q11.2;p11.2)dn		Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 14 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ROBO2	Orphanet:289365	Familial vesicoureteral reflux
TAF4B	Orphanet:399805	Male infertility with azoospermia or oligozoospermia due to single gene mutation
NTNG2	Orphanet:528084	Non-specific syndromic intellectual disability
LUZP1	Orphanet:1606	1p36 deletion syndrome
STAMBP	Orphanet:294016	Microcephaly-capillary malformation syndrome
MUCL3	Orphanet:171700	Diffuse panbronchiolitis
ERBB4	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
ERBB4	Orphanet:803	Amyotrophic lateral sclerosis
EYA1	Orphanet:107	BOR syndrome
EYA1	Orphanet:2792	Otofaciocervical syndrome
EYA1	Orphanet:52429	Branchiootic syndrome
KCNMA1	Orphanet:664438	Gingival fibromatosis-aortic root dilatation-facial dysmorphism-intellectual disability syndrome
KCNMA1	Orphanet:79137	Generalized epilepsy-paroxysmal dyskinesia syndrome
RARB	Orphanet:689829	Microphthalmia-motor delay-language delay-brain anomalies-diaphragmatic hernia syndrome

Cohort genes → proteins

27 cohort genes, 24 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	27

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ROBO2	HGNC:10250	ENSG00000185008	Q9HCK4	Roundabout homolog 2	gwas
TAF4B	HGNC:11538	ENSG00000141384	Q92750	Transcription initiation factor TFIID subunit 4B	gwas
C4BPA	HGNC:1325	ENSG00000123838	P04003	C4b-binding protein alpha chain	gwas
NTNG2	HGNC:14288	ENSG00000196358	Q96CW9	Netrin-G2	gwas
LUZP1	HGNC:14985	ENSG00000169641	Q86V48	Leucine zipper protein 1	gwas
HTATIP2	HGNC:16637	ENSG00000109854	Q9BUP3	Protein HTATIP2	gwas
STAMBP	HGNC:16950	ENSG00000124356	O95630	STAM-binding protein	gwas
MUCL3	HGNC:21666	ENSG00000168631	Q3MIW9	Mucin-like protein 3	gwas
MORN4	HGNC:24001	ENSG00000171160	Q8NDC4	MORN repeat-containing protein 4	gwas
FNDC3B	HGNC:24670	ENSG00000075420	Q53EP0	Fibronectin type III domain-containing protein 3B	gwas
TTC23	HGNC:25730	ENSG00000103852	Q5W5X9	Tetratricopeptide repeat protein 23	gwas
LIME1	HGNC:26016	ENSG00000203896	Q9H400	Lck-interacting transmembrane adapter 1	gwas
LINC00927	HGNC:27522	ENSG00000259361		long intergenic non-protein coding RNA 927	gwas
DISC1	HGNC:2888	ENSG00000162946	Q9NRI5	Disrupted in schizophrenia 1 protein	gwas
PATJ	HGNC:28881	ENSG00000132849	Q8NI35	InaD-like protein	gwas
DNAH8	HGNC:2952	ENSG00000124721	Q96JB1	Dynein axonemal heavy chain 8	gwas
DOK1	HGNC:2990	ENSG00000115325	Q99704	Docking protein 1	gwas
SLC41A3	HGNC:31046	ENSG00000114544	Q96GZ6	Solute carrier family 41 member 3	gwas
ERBB4	HGNC:3432	ENSG00000178568	Q15303	Receptor tyrosine-protein kinase erbB-4	gwas
EYA1	HGNC:3519	ENSG00000104313	Q99502	Protein phosphatase EYA1	gwas
MIR1207	HGNC:35273	ENSG00000221176		microRNA 1207	gwas
FARP1	HGNC:3591	ENSG00000152767	Q9Y4F1	FERM, ARHGEF and pleckstrin domain-containing protein 1	gwas
KCNMA1	HGNC:6284	ENSG00000156113	Q12791	Calcium-activated potassium channel subunit alpha-1	gwas
MAGED1	HGNC:6813	ENSG00000179222	Q9Y5V3	Melanoma-associated antigen D1	gwas
MGST1	HGNC:7061	ENSG00000008394	P10620	Microsomal glutathione S-transferase 1	gwas
PVT1	HGNC:9709	ENSG00000249859		Pvt1 oncogene	gwas
RARB	HGNC:9865	ENSG00000077092	P10826	Retinoic acid receptor beta	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ROBO2	Roundabout homolog 2	Receptor for SLIT2, and probably SLIT1, which are thought to act as molecular guidance cue in cellular migration, including axonal navigation at the ventral midline of the neural tube and projection of axons to different regions during neu…
TAF4B	Transcription initiation factor TFIID subunit 4B	Cell type-specific subunit of the general transcription factor TFIID that may function as a gene-selective coactivator in certain cells.
C4BPA	C4b-binding protein alpha chain	Controls the classical pathway of complement activation.
NTNG2	Netrin-G2	Involved in controlling patterning and neuronal circuit formation at the laminar, cellular, subcellular and synaptic levels.
LUZP1	Leucine zipper protein 1	F-actin cross-linking protein.
HTATIP2	Protein HTATIP2	Represses translation by preventing reactivation of elongation factor eEF1A.
STAMBP	STAM-binding protein	Zinc metalloprotease that specifically cleaves ‘Lys-63’-linked polyubiquitin chains.
MUCL3	Mucin-like protein 3	May modulate NF-kappaB signaling and play a role in cell growth.
MORN4	MORN repeat-containing protein 4	Plays a role in promoting axonal degeneration following neuronal injury by toxic insult or trauma.
FNDC3B	Fibronectin type III domain-containing protein 3B	May be a positive regulator of adipogenesis.
TTC23	Tetratricopeptide repeat protein 23	Participates positively in the ciliary Hedgehog (Hh) signaling.
LIME1	Lck-interacting transmembrane adapter 1	Involved in BCR (B-cell antigen receptor)-mediated signaling in B-cells and TCR (T-cell antigen receptor)-mediated T-cell signaling in T-cells.
DISC1	Disrupted in schizophrenia 1 protein	Involved in the regulation of multiple aspects of embryonic and adult neurogenesis.
PATJ	InaD-like protein	Scaffolding protein that facilitates the localization of proteins to the cell membrane.
DNAH8	Dynein axonemal heavy chain 8	Force generating protein component of the outer dynein arms (ODAs) in the sperm flagellum.
DOK1	Docking protein 1	DOK proteins are enzymatically inert adaptor or scaffolding proteins.
SLC41A3	Solute carrier family 41 member 3	Na(+)/Mg(2+) ion exchanger that acts as a predominant Mg(2+) efflux system at the mitochondrial inner membrane.
ERBB4	Receptor tyrosine-protein kinase erbB-4	Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins and EGF family members and regulates development of the heart, the central nervous system and the mammary gland, gene transcription, cell prolife…
EYA1	Protein phosphatase EYA1	Functions both as protein phosphatase and as transcriptional coactivator for SIX1, and probably also for SIX2, SIX4 and SIX5.
FARP1	FERM, ARHGEF and pleckstrin domain-containing protein 1	Functions as a guanine nucleotide exchange factor for RAC1.
KCNMA1	Calcium-activated potassium channel subunit alpha-1	Potassium channel activated by both membrane depolarization or increase in cytosolic Ca(2+) that mediates export of K(+).
MAGED1	Melanoma-associated antigen D1	Involved in the apoptotic response after nerve growth factor (NGF) binding in neuronal cells.
MGST1	Microsomal glutathione S-transferase 1	Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.
RARB	Retinoic acid receptor beta	Receptor for retinoic acid.

Protein-family classification

Druggable: 6 · Difficult: 3 · Unknown: 18 · Druggable fraction: 0.22

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Nuclear receptor	1	14.3×	0.275
Complement	1	9.9×	0.275
Ion channel	1	4.1×	0.275
Antibody/Immunoglobulin	2	2.2×	0.275
Scaffold/PPI	3	1.9×	0.275
Other/Unknown	18	1.2×	0.275
Kinase	1	1.0×	0.629

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ROBO2	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom
TAF4B	Other/Unknown	no		TAFH_NHR1, TAF4_C, Histone-fold
C4BPA	Complement	yes		Sushi_SCR_CCP_dom, Sushi/SCR/CCP_sf, C4bp_oligo
NTNG2	Other/Unknown	no		EGF, LE_dom, Laminin_N
LUZP1	Other/Unknown	no		Cortactin-Actin_Reg
HTATIP2	Other/Unknown	no		NAD(P)-bd_dom, NAD(P)-bd_dom_sf
STAMBP	Other/Unknown	no		JAMM/MPN+_dom, USP8_dimer, MPN
MUCL3	Other/Unknown	no		MUCL3
MORN4	Other/Unknown	no		MORN, MORN4
FNDC3B	Antibody/Immunoglobulin	yes		FN3_dom, Ig-like_fold, FN3_sf
TTC23	Other/Unknown	no		TPR-like_helical_dom_sf, TPR_rpt, TTC23/TTC23L
LIME1	Other/Unknown	no		Lime1
LINC00927	Other/Unknown	no
DISC1	Other/Unknown	no		DISC1
PATJ	Scaffold/PPI	no		PDZ, L27_dom, L27_2
DNAH8	Other/Unknown	no		AAA+_ATPase, Dhc_D6_P-loop, Dynein_heavy_tail
DOK1	Scaffold/PPI	no		PH_domain, IRS_PTB, PH-like_dom_sf
SLC41A3	Other/Unknown	no		SLC41_membr_dom, SLC41_membr_dom_sf, SLC41A1-3
ERBB4	Kinase	yes	2.7.10.1	Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
EYA1	Other/Unknown	no		EYA_dom, EYA, EYA_dom_sf
MIR1207	Other/Unknown	no
FARP1	Scaffold/PPI	no		DH_dom, FERM_domain, Ez/rad/moesin-like
KCNMA1	Ion channel	yes		RCK_N, K_chnl_BK_asu, Ion_trans_dom
MAGED1	Other/Unknown	no		MHD_dom, MAGE, MAGE_WH1
MGST1	Other/Unknown	no		Membr-assoc_MAPEG, MAPEG-like_dom_sf, MGST1-like
PVT1	Other/Unknown	no
RARB	Nuclear receptor	yes		Nucl_hrmn_rcpt_lig-bd, Znf_hrmn_rcpt, Nuclear_hrmn_rcpt

Expression context

Cohort genes with no expression data: 0.

26 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	27
unknown	0

Top tissues across cohort

Tissue	Cohort genes
buccal mucosa cell	3
lower esophagus mucosa	3
adrenal tissue	3
cortical plate	2
ganglionic eminence	2
ventricular zone	2
secondary oocyte	2
liver	2
right lobe of liver	2
monocyte	2
pancreatic ductal cell	2
sperm	2
tendon of biceps brachii	2
tibia	2
renal medulla	2
choroid plexus epithelium	2
stromal cell of endometrium	2
oocyte	1
lower lobe of lung	1
leukocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ROBO2	192	broad	marker	ganglionic eminence, cortical plate, ventricular zone
TAF4B	243	ubiquitous	marker	secondary oocyte, buccal mucosa cell, oocyte
C4BPA	166	tissue_specific	marker	right lobe of liver, liver, lower lobe of lung
NTNG2	173	broad	marker	pancreatic ductal cell, monocyte, leukocyte
LUZP1	290	ubiquitous	marker	tendon of biceps brachii, sperm, male germ cell
HTATIP2	292	ubiquitous	marker	jejunal mucosa, colonic mucosa, duodenum
STAMBP	292	ubiquitous	marker	C1 segment of cervical spinal cord, spinal cord, corpus callosum
MUCL3	51	tissue_specific	marker	mucosa of stomach, lower esophagus mucosa, body of stomach
MORN4	220	ubiquitous	marker	cortical plate, hypothalamus, prefrontal cortex
FNDC3B	275	ubiquitous	marker	cartilage tissue, calcaneal tendon, tibia
TTC23	189	ubiquitous	marker	lower esophagus muscularis layer, lower esophagus, muscle layer of sigmoid colon
LIME1	138	broad	marker	granulocyte, right lobe of liver, liver
LINC00927	66	tissue_specific	marker	left testis, right testis, testis
DISC1	207	ubiquitous	marker	buccal mucosa cell, sural nerve, decidua
PATJ	273	ubiquitous	marker	heart right ventricle, lower esophagus mucosa, renal medulla
DNAH8	68	tissue_specific	marker	sperm, male germ line stem cell (sensu Vertebrata) in testis, adult organism
DOK1	269	ubiquitous	marker	tendon of biceps brachii, pancreatic ductal cell, monocyte
SLC41A3	273	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
ERBB4	226	broad	marker	endothelial cell, secondary oocyte, cranial nerve II
EYA1	205	broad	marker	choroid plexus epithelium, urethra, mucosa of paranasal sinus
MIR1207	31		yes	blood, gastrocnemius, adrenal tissue
FARP1	283	ubiquitous	marker	renal medulla, stromal cell of endometrium, adrenal tissue
KCNMA1	275	ubiquitous	marker	parotid gland, saphenous vein, tibia
MAGED1	290	ubiquitous	marker	ventricular zone, stromal cell of endometrium, ganglionic eminence
MGST1	258	ubiquitous	marker	right adrenal gland, right adrenal gland cortex, left adrenal gland
PVT1	227	ubiquitous	marker	lower esophagus mucosa, adrenal tissue, colonic epithelium
RARB	210	ubiquitous	marker	choroid plexus epithelium, palpebral conjunctiva, buccal mucosa cell

Protein interactions among cohort

Intra-cohort edges: 4.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PATJ	5,189
ERBB4	4,325
STAMBP	3,664
DISC1	3,573
KCNMA1	2,606
HTATIP2	2,290
RARB	2,185
ROBO2	2,181
MAGED1	1,976
EYA1	1,806

Intra-cohort edges

A	B	Sources
DISC1	FNDC3B	intact
DISC1	RARB	intact
MAGED1	TTC23	biogrid_interaction, intact
NTNG2	ROBO2	string_interaction

Structural data

PDB: 12 · AlphaFold-only: 12 · No structure: 3

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KCNMA1	Q12791	36
ERBB4	Q15303	14
PATJ	Q8NI35	10
C4BPA	P04003	9
RARB	P10826	9
ROBO2	Q9HCK4	6
STAMBP	O95630	5
NTNG2	Q96CW9	3
HTATIP2	Q9BUP3	1
DISC1	Q9NRI5	1
DOK1	Q99704	1
FARP1	Q9Y4F1	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MORN4	Q8NDC4	97.33
TTC23	Q5W5X9	85.44
SLC41A3	Q96GZ6	79.10
MGST1	P10620	78.65
FNDC3B	Q53EP0	75.78
EYA1	Q99502	66.68
LUZP1	Q86V48	57.40
TAF4B	Q92750	56.15
LIME1	Q9H400	54.39
MAGED1	Q9Y5V3	51.21
MUCL3	Q3MIW9	47.09
DNAH8	Q96JB1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 106. Enrichment computed across 27 evidence-associated genes (14 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 14 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Formation of the ureteric bud	2	70.9×	0.037	ROBO2, EYA1
Regulation of cortical dendrite branching	1	163.1×	0.105	ROBO2
Acetylcholine inhibits contraction of outer hair cells	1	163.1×	0.105	KCNMA1
SARS-CoV-2 targets PDZ proteins in cell-cell junction	1	163.1×	0.105	PATJ
Caspase activation via extrinsic apoptotic signalling pathway	1	102.0×	0.105	MAGED1
PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1	1	90.6×	0.105	DOK1
ROBO receptors bind AKAP5	1	90.6×	0.105	ROBO2
Downregulation of ERBB4 signaling	1	81.6×	0.105	ERBB4
Ca2+ activated K+ channels	1	81.6×	0.105	KCNMA1
Caspase activation via Dependence Receptors in the absence of ligand	1	81.6×	0.105	MAGED1
PI3K events in ERBB4 signaling	1	74.2×	0.105	ERBB4
Regulation of commissural axon pathfinding by SLIT and ROBO	1	68.0×	0.105	ROBO2
Nitric oxide stimulates guanylate cyclase	1	58.3×	0.105	KCNMA1
ERBB2 Activates PTK6 Signaling	1	58.3×	0.105	ERBB4
Kidney development	1	58.3×	0.105	ROBO2
SHC1 events in ERBB4 signaling	1	51.0×	0.105	ERBB4
cGMP effects	1	51.0×	0.105	KCNMA1
ERBB2 Regulates Cell Motility	1	51.0×	0.105	ERBB4
PI3K events in ERBB2 signaling	1	48.0×	0.105	ERBB4
Complement cascade	1	45.3×	0.105	C4BPA
GRB2 events in ERBB2 signaling	1	45.3×	0.105	ERBB4
Aflatoxin activation and detoxification	1	45.3×	0.105	MGST1
Glutathione conjugation	1	35.5×	0.114	MGST1
NPAS4 regulates expression of target genes	1	35.5×	0.114	MAGED1
SHC1 events in ERBB2 signaling	1	34.0×	0.114	ERBB4
Long-term potentiation	1	34.0×	0.114	ERBB4
Signaling by ERBB2 TMD/JMD mutants	1	34.0×	0.114	ERBB4
Signaling by ERBB2 KD Mutants	1	30.2×	0.123	ERBB4
Signaling by Retinoic Acid	1	29.1×	0.124	RARB
Downregulation of ERBB2 signaling	1	27.2×	0.126	ERBB4

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 22 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
neural fold bending	1	766.0×	0.037	LUZP1
contractile ring contraction	1	766.0×	0.037	LUZP1
cellular response to lipid hydroperoxide	1	766.0×	0.037	MGST1
otic vesicle morphogenesis	1	766.0×	0.037	EYA1
outflow tract septum morphogenesis	2	58.9×	0.037	ROBO2, RARB
regulation of presynapse assembly	2	49.4×	0.037	NTNG2, FARP1
metanephros development	2	46.4×	0.037	ROBO2, EYA1
ureteric bud development	2	41.4×	0.037	ROBO2, RARB
central nervous system morphogenesis	1	383.0×	0.038	ERBB4
mitochondrial magnesium ion transmembrane transport	1	383.0×	0.038	SLC41A3
establishment of planar polarity involved in nephron morphogenesis	1	383.0×	0.038	ERBB4
regulation of opsonization	1	383.0×	0.038	C4BPA
pyramidal neuron migration to cerebral cortex	1	255.3×	0.038	DISC1
olfactory bulb interneuron development	1	255.3×	0.038	ROBO2
response to carbon monoxide	1	255.3×	0.038	KCNMA1
glutathione transport	1	255.3×	0.038	MGST1
macrophage colony-stimulating factor signaling pathway	1	255.3×	0.038	DOK1
negative regulation of negative chemotaxis	1	255.3×	0.038	ROBO2
micturition	1	255.3×	0.038	KCNMA1
positive regulation of secondary heart field cardioblast proliferation	1	255.3×	0.038	EYA1
retrograde trans-synaptic signaling by trans-synaptic protein complex	1	255.3×	0.038	FARP1
cell surface receptor signaling pathway via JAK-STAT	2	26.4×	0.038	STAMBP, ERBB4
positive regulation of epithelial cell proliferation	2	22.2×	0.038	ERBB4, EYA1
synapse assembly	2	21.0×	0.038	ERBB4, FARP1
striated muscle tissue development	1	191.5×	0.040	EYA1
smooth muscle contraction involved in micturition	1	191.5×	0.040	KCNMA1
cardiac muscle tissue regeneration	1	191.5×	0.040	ERBB4
apoptotic process involved in luteolysis	1	191.5×	0.040	ROBO2
postsynaptic specialization assembly	1	191.5×	0.040	NTNG2
glandular epithelial cell development	1	153.2×	0.040	RARB

Therapeutics

Drugs indicated or in trials for this disease

No drug has an approved disease-direct ChEMBL indication for this disease.

2 drugs in clinical trials for this disease (phase 2–3, investigational): efficacy not established — a trial record, not an indication.

Drug	Highest phase
Methylprednisolone	Phase 3
Prednisone	Phase 2

Drug target analysis

Approved (phase 4): 3 · Phase ≥3: 3 · Phased (≥1): 3 · Undrugged: 24

Druggability breadth: 7 of 27 evidence-associated genes (26%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
ERBB4	MOBOCERTINIB
KCNMA1	CANNABIDIOL
RARB	BEXAROTENE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ERBB4	47	4
RARB	18	4
KCNMA1	2	4
ROBO2	0	0
TAF4B	0	0
C4BPA	0	0
NTNG2	0	0
LUZP1	0	0
HTATIP2	0	0
STAMBP	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOBOCERTINIB	4	ERBB4
AFATINIB	4	ERBB4
FEDRATINIB	4	ERBB4
NERATINIB	4	ERBB4
IBRUTINIB	4	ERBB4
AFATINIB DIMALEATE	4	ERBB4
DACOMITINIB	4	ERBB4
DACOMITINIB ANHYDROUS	4	ERBB4
VANDETANIB	4	ERBB4
BOSUTINIB	4	ERBB4
BRIGATINIB	4	ERBB4
ACALABRUTINIB	4	ERBB4
ZANUBRUTINIB	4	ERBB4
TIRABRUTINIB	4	ERBB4
RITLECITINIB	4	ERBB4
DASATINIB	4	ERBB4
ERLOTINIB	4	ERBB4
LAPATINIB	4	ERBB4
MIDOSTAURIN	4	ERBB4
GEFITINIB	4	ERBB4
CANNABIDIOL	4	KCNMA1
BEXAROTENE	4	RARB
AMOXICILLIN	4	RARB
ADAPALENE	4	RARB
TOLCAPONE	4	RARB
KETOCONAZOLE	4	RARB
CYCLOSPORINE	4	RARB
TAZAROTENE	4	RARB
TAMIBAROTENE	4	RARB
TRIFAROTENE	4	RARB

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
ERBB4	591	Binding:579, ADMET:8, Functional:4
RARB	278	Binding:199, Functional:78, ADMET:1
KCNMA1	94	Binding:91, Functional:2, Toxicity:1
LUZP1	6	Binding:6
MGST1	3	ADMET:2, Binding:1
STAMBP	2	Binding:2
MAGED1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ERBB4	2.7.10.1	receptor protein-tyrosine kinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
ERBB4	591
RARB	278

Pharmacogenomics

Cohort genes with a PharmGKB record: 26; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

30 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
MOBOCERTINIB	4	ERBB4
AFATINIB	4	ERBB4
FEDRATINIB	4	ERBB4
NERATINIB	4	ERBB4
IBRUTINIB	4	ERBB4
AFATINIB DIMALEATE	4	ERBB4
DACOMITINIB	4	ERBB4
DACOMITINIB ANHYDROUS	4	ERBB4
VANDETANIB	4	ERBB4
BOSUTINIB	4	ERBB4
BRIGATINIB	4	ERBB4
ACALABRUTINIB	4	ERBB4
ZANUBRUTINIB	4	ERBB4
TIRABRUTINIB	4	ERBB4
RITLECITINIB	4	ERBB4
DASATINIB	4	ERBB4
ERLOTINIB	4	ERBB4
LAPATINIB	4	ERBB4
MIDOSTAURIN	4	ERBB4
GEFITINIB	4	ERBB4
CANNABIDIOL	4	KCNMA1
BEXAROTENE	4	RARB
AMOXICILLIN	4	RARB
ADAPALENE	4	RARB
TOLCAPONE	4	RARB
KETOCONAZOLE	4	RARB
CYCLOSPORINE	4	RARB
TAZAROTENE	4	RARB
TAMIBAROTENE	4	RARB
TRIFAROTENE	4	RARB

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	3	ERBB4, KCNMA1, RARB
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	2	ROBO2, C4BPA
D	Druggable family + AlphaFold only, no drug	1	FNDC3B
E	Difficult family or no structure, no drug	21	TAF4B, NTNG2, LUZP1, HTATIP2, STAMBP, MUCL3, MORN4, TTC23, LIME1, LINC00927 (+11 more)

Undrugged target profiles

24 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
ROBO2	0	—
TAF4B	0	—
C4BPA	0	—
NTNG2	0	—
LUZP1	6	—
HTATIP2	0	—
STAMBP	2	—
MUCL3	0	—
MORN4	0	—
FNDC3B	0	—
TTC23	0	—
LIME1	0	—
LINC00927	0	—
DISC1	0	—
PATJ	0	—
DNAH8	0	—
DOK1	0	—
SLC41A3	0	—
EYA1	0	—
MIR1207	0	—
FARP1	0	—
MAGED1	1	—
MGST1	3	—
PVT1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 26.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	20
PHASE4	2
PHASE2/PHASE3	1
PHASE3	1
PHASE1	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00510263	PHASE4	COMPLETED	Scandinavian Bell’s Palsy Study
NCT05167760	PHASE4	WITHDRAWN	Efficacy of Topical Apraclonidine for the Treatment of Ocular Synkinesis
NCT07116811	PHASE3	NOT_YET_RECRUITING	Steroids for Facial Nerve Function Protection in Post-surgical Vestibular Schwannoma Patients
NCT03508440	PHASE2/PHASE3	COMPLETED	Intratympanic Steroid for Bell’s Palsy
NCT03496025	PHASE1	UNKNOWN	Facial Function Reanimation by Electrical Pacing in Unilateral Facial Paralysis.
NCT06895902	EARLY_PHASE1	RECRUITING	Suture Lid Spring for Lid Closure in Patients With Facial Nerve Palsy
NCT06542289	Not specified	NOT_YET_RECRUITING	Safety and Effectiveness of the BlinkER System in Participants With Facial Nerve Palsy
NCT07266636	Not specified	NOT_YET_RECRUITING	Effects of Photobiomodulation and Electrical Stimulation Among Bell’s Palsy Patients
NCT07436624	Not specified	ACTIVE_NOT_RECRUITING	Kabat Rehabilitation Versus Kinesiology Taping in Bell’s Palsy
NCT07537426	Not specified	RECRUITING	The Efficacy of Intradermal Acupuncture for Ocular Surface Diseases After Intractable Facial Paralysis
NCT07573358	Not specified	NOT_YET_RECRUITING	Validation of Artificial Intelligence-Based Facial Paralysis Assessment in Patients With Bell’s Palsy
NCT07598175	Not specified	NOT_YET_RECRUITING	Study on the Optimal Waveform Patterns of Electroacupuncture Targeted Intervention for Bell’s Palsy Based on Surface Electromyography Characteristics
NCT00608660	Not specified	COMPLETED	Randomized Controlled Trial of Acupuncture to Treat Bell’s Palsy According to Different Stages
NCT00685789	Not specified	COMPLETED	Acupuncture With Deqi And Psychological Effects in Treatment of Bell’s Palsy
NCT01201642	Not specified	UNKNOWN	Prednisone and Acupuncture for the Treatment of Facial Neuritis: a Multiple Center, CER in China
NCT01377766	Not specified	UNKNOWN	The Relationship Between Psychological Factors and Bell’s Palsy
NCT01686464	Not specified	COMPLETED	A Clinical Study on the Combined Magnetic and Oxygen Treatment for Bell’s Palsy
NCT02489162	Not specified	COMPLETED	The Role of a Device to Evaluate the Neuromuscular Function in Assessing Muscle in Facial Paralysis Patients
NCT03469427	Not specified	UNKNOWN	Multislice Computed Tomography in Cases With Facial Nerve Paralysis Due to Temporal Bone Trauma
NCT04353908	Not specified	COMPLETED	Collagen Treatment in Facial Nerve Palsy
NCT04894513	Not specified	COMPLETED	Electro Physiological Responses to Kabat Motor Control Re-education on Bell’s Palsy: A Randomized Controlled Study
NCT05504473	Not specified	COMPLETED	Blink Restoration in Patients With Facial Nerve Palsy
NCT05585346	Not specified	COMPLETED	Photobiomodulation Therapy for Idiopathic Facial Paralysis
NCT05707091	Not specified	UNKNOWN	Low Laser Therapy on Facial Motor Functions Function and Synkinesis in Patients With Bell’s Palsy
NCT06083389	Not specified	UNKNOWN	Kabat Rehabilitation Technique Versus Conventional Physical Therapy in Treatment of Bell’s Palsy
NCT06280794	Not specified	UNKNOWN	Efficacy of Laser Acupuncture for Idiopathic Bell’s Palsy

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
APRACLONIDINE	4	3
PREDNISOLONE	4	2
THIAMINE ION	4	2
VALACYCLOVIR	4	1
METHOPRENE	2	1