PRPH

Summary

PRPH (peripherin, HGNC:9461) is a protein-coding gene on chromosome 12q13.12, encoding Peripherin (P41219). Class-III neuronal intermediate filament protein.

This gene encodes a cytoskeletal protein found in neurons of the peripheral nervous system. The encoded protein is a type III intermediate filament protein with homology to other cytoskeletal proteins such as desmin, and is a different protein that the peripherin found in photoreceptors. Mutations in this gene have been associated with susceptibility to amyotrophic lateral sclerosis.

Source: NCBI Gene 5630 — RefSeq curated summary.

At a glance

• Gene–disease (curated): amyotrophic lateral sclerosis type 1 (Moderate, GenCC) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 95 total — 2 likely-pathogenic
• GTEx eGene: eQTL in 27 tissues, sQTL in 0 (q < 0.05)
• Phenotypes (HPO): 55
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.16 (unconstrained)
• MANE Select transcript: NM_006262
• Notable: 95 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9461
Approved symbol	PRPH
Name	peripherin
Location	12q13.12
Locus type	gene with protein product
Status	Approved
Aliases	PRPH1
Ensembl gene	ENSG00000135406
Ensembl biotype	protein_coding
OMIM	170710
Entrez	5630

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 3 retained_intron

MANE Select: ENST00000257860

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 1, TSL 3: 1, TSL 5: 3

ENST00000257860, ENST00000451891, ENST00000530631, ENST00000532332, ENST00000533401, ENST00000537252, ENST00001137731

RefSeq mRNA: 1 — MANE Select: NM_006262 NM_006262

CCDS: CCDS8783

Canonical transcript exons

ENST00000257860 — 9 exons

Exon	Start	End
ENSE00001279489	49298288	49298686
ENSE00001279494	49295147	49295745
ENSE00003498876	49296178	49296238
ENSE00003501393	49297148	49297273
ENSE00003506308	49297357	49297577
ENSE00003521805	49297677	49297726
ENSE00003529345	49296889	49297056
ENSE00003572461	49296432	49296527
ENSE00003578225	49297958	49298037

Expression profiles

Bgee: expression breadth ubiquitous, 178 present calls, max score 99.50.

FANTOM5 (CAGE): breadth broad, TPM avg 3.5098 / max 1095.3849, expressed in 271 samples.

Highest expression (Bgee): dorsal root ganglion, trigeminal ganglion, sperm, male germ cell, testis.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PRPH is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 27 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 27 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Brain Hypothalamus	eqtl	7.6e-13	+0.64	12:49294274:T:C
Brain Spinal cord cervical c-1	eqtl	7.2e-09	+0.58	12:49294274:T:C
Nerve Tibial	eqtl	1.2e-07	-0.49	12:49293595:G:A
Spleen	eqtl	5.3e-07	-0.91	12:49284707:G:A
Brain Hippocampus	eqtl	1.2e-06	+0.51	12:49278836:C:A
Skin Sun Exposed Lower leg	eqtl	2.1e-06	-0.44	12:49293595:G:A
Skin Not Sun Exposed Suprapubic	eqtl	1.4e-05	-0.48	12:49293595:G:A
Lung	eqtl	2.5e-05	-0.50	12:49293595:G:A
Brain Cerebellar Hemisphere	eqtl	4.5e-05	-0.40	12:49279768:G:C
Adipose Visceral Omentum	eqtl	4.7e-05	-0.35	12:49293595:G:A
Brain Cerebellum	eqtl	2.6e-04	-0.46	12:49279768:G:C
Muscle Skeletal	eqtl	3.0e-04	-0.42	12:49284707:G:A
Brain Caudate basal ganglia	eqtl	3.4e-04	+0.34	12:49291306:T:C
Artery Tibial	eqtl	5.6e-04	-0.33	12:49293595:G:A
Colon Sigmoid	eqtl	7.0e-04	-0.47	12:49584282:A:T
Adipose Subcutaneous	eqtl	2.0e-03	-0.29	12:49293595:G:A
Artery Coronary	eqtl	3.3e-03	-0.60	12:49293595:G:A
Esophagus Mucosa	eqtl	3.5e-03	-0.60	12:49207259:C:T
Heart Left Ventricle	eqtl	3.6e-03	-0.82	12:49426892:T:C
Brain Substantia nigra	eqtl	3.6e-03	+0.45	12:49282227:T:C

FANTOM5 promoters

8 alternative TSS:

Promoter ID	TPM avg	Samples expressed
125316	3.2967	249
125318	0.0486	4
125315	0.0478	20
125320	0.0410	10
125314	0.0403	16
125321	0.0136	5
125319	0.0130	5
125317	0.0089	4

Top tissues by expression

showing 100 of 293 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
dorsal root ganglion	UBERON:0000044	99.50	gold quality
trigeminal ganglion	UBERON:0001675	97.43	gold quality
sperm	CL:0000019	96.73	gold quality
male germ cell	CL:0000015	95.78	gold quality
left testis	UBERON:0004533	93.48	gold quality
right testis	UBERON:0004534	93.23	gold quality
testis	UBERON:0000473	91.29	gold quality
muscle layer of sigmoid colon	UBERON:0035805	90.34	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.41	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.58	gold quality
cranial nerve II	UBERON:0000941	88.08	gold quality
sympathetic trunk	UBERON:0000407	86.36	gold quality
right uterine tube	UBERON:0001302	86.15	gold quality
sigmoid colon	UBERON:0001159	85.35	gold quality
transverse colon	UBERON:0001157	82.34	gold quality
colon	UBERON:0001155	81.90	gold quality
large intestine	UBERON:0000059	81.57	gold quality
caecum	UBERON:0001153	81.47	gold quality
mucosa of stomach	UBERON:0001199	81.36	gold quality
type B pancreatic cell	CL:0000169	80.90	gold quality
olfactory bulb	UBERON:0002264	80.80	gold quality
intestine	UBERON:0000160	80.53	gold quality
adult organism	UBERON:0007023	80.48	gold quality
vena cava	UBERON:0004087	80.23	gold quality
vermiform appendix	UBERON:0001154	80.13	gold quality
diaphragm	UBERON:0001103	79.68	gold quality
mucosa of urinary bladder	UBERON:0001259	79.10	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	78.55	gold quality
small intestine	UBERON:0002108	77.57	gold quality
small intestine Peyer’s patch	UBERON:0003454	77.51	gold quality
lower esophagus muscularis layer	UBERON:0035833	77.51	gold quality
rectum	UBERON:0001052	77.49	gold quality
lower esophagus	UBERON:0013473	77.27	gold quality
mucosa of paranasal sinus	UBERON:0005030	77.22	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	77.01	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	76.89	gold quality
medulla oblongata	UBERON:0001896	76.87	silver quality
tendon	UBERON:0000043	76.82	gold quality
cervix squamous epithelium	UBERON:0006922	76.12	gold quality
spinal cord	UBERON:0002240	75.78	gold quality
calcaneal tendon	UBERON:0003701	75.74	gold quality
superior vestibular nucleus	UBERON:0007227	75.71	silver quality
oocyte	CL:0000023	75.62	gold quality
mucosa of transverse colon	UBERON:0004991	75.61	gold quality
pons	UBERON:0000988	75.42	gold quality
epithelial cell of pancreas	CL:0000083	75.34	gold quality
ventral tegmental area	UBERON:0002691	75.24	gold quality
inferior olivary complex	UBERON:0002127	75.19	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	74.96	gold quality
colonic epithelium	UBERON:0000397	74.63	gold quality
subthalamic nucleus	UBERON:0001906	74.41	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	74.32	gold quality
thymus	UBERON:0002370	74.18	silver quality
tendon of biceps brachii	UBERON:0008188	74.14	silver quality
fundus of stomach	UBERON:0001160	74.07	gold quality
vastus lateralis	UBERON:0001379	74.04	gold quality
dorsal plus ventral thalamus	UBERON:0001897	73.96	gold quality
quadriceps femoris	UBERON:0001377	73.85	gold quality
islet of Langerhans	UBERON:0000006	73.67	gold quality
saphenous vein	UBERON:0007318	73.56	gold quality
hair follicle	UBERON:0002073	73.52	gold quality
trachea	UBERON:0003126	73.41	gold quality
left uterine tube	UBERON:0001303	73.37	gold quality
nipple	UBERON:0002030	73.34	gold quality
body of tongue	UBERON:0011876	73.24	gold quality
superior surface of tongue	UBERON:0007371	73.12	gold quality
pharyngeal mucosa	UBERON:0000355	73.08	gold quality
lateral globus pallidus	UBERON:0002476	73.04	gold quality
inferior vagus X ganglion	UBERON:0005363	72.98	gold quality
smooth muscle tissue	UBERON:0001135	72.97	gold quality
pericardium	UBERON:0002407	72.96	gold quality
tongue	UBERON:0001723	72.93	gold quality
substantia nigra pars reticulata	UBERON:0001966	72.91	gold quality
substantia nigra pars compacta	UBERON:0001965	72.90	gold quality
lateral nuclear group of thalamus	UBERON:0002736	72.90	gold quality
vagina	UBERON:0000996	72.79	gold quality
coronary artery	UBERON:0001621	72.52	gold quality
endometrium epithelium	UBERON:0004811	72.37	gold quality
left coronary artery	UBERON:0001626	72.30	gold quality
endocervix	UBERON:0000458	72.29	gold quality
omental fat pad	UBERON:0010414	72.09	gold quality
peritoneum	UBERON:0002358	72.08	gold quality
myocardium	UBERON:0002349	71.93	gold quality
nasal cavity mucosa	UBERON:0001826	71.88	gold quality
subcutaneous adipose tissue	UBERON:0002190	71.88	gold quality
right coronary artery	UBERON:0001625	71.73	gold quality
epithelium of nasopharynx	UBERON:0001951	71.63	gold quality
adipose tissue of abdominal region	UBERON:0007808	71.57	gold quality
penis	UBERON:0000989	71.23	silver quality
endothelial cell	CL:0000115	71.16	gold quality
duodenum	UBERON:0002114	71.16	gold quality
renal medulla	UBERON:0000362	71.12	gold quality
urethra	UBERON:0000057	71.00	gold quality
cerebellar vermis	UBERON:0004720	70.95	gold quality
seminal vesicle	UBERON:0000998	70.66	silver quality
jejunum	UBERON:0002115	70.56	silver quality
secondary oocyte	CL:0000655	70.30	gold quality
tongue squamous epithelium	UBERON:0006919	70.28	gold quality
deltoid	UBERON:0001476	70.26	gold quality
pituitary gland	UBERON:0000007	70.09	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-56	yes	4182.72
E-MTAB-11121	yes	1446.01
E-HCAD-10	yes	4.32
E-GEOD-125970	no	3.23
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 73 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Spinal cord	tissue	346.7
Medulla oblongata	tissue	45.1
Substantia nigra	tissue	21.1
Superior colliculi	tissue	14.6
Adrenal gland	tissue	13.7	medium
Pons	tissue	12.5
Midbrain	tissue	10.7
Vagina	tissue	10.6	not detected
Thalamus	tissue	10.0
Small intestine	tissue	8.4	not detected
Appendix	tissue	7.1	not detected
Testis	tissue	6.6	low
Hypothalamus	tissue	6.1
Locus coeruleus	tissue	6.0
Periaqueductal gray	tissue	5.8
Colon	tissue	4.6	high
Duodenum	tissue	4.5	not detected
Pituitary gland	tissue	3.7
Cerebral cortex	tissue	2.7	not detected
Somatosensory cortex	tissue	2.7
Ventral forebrain	tissue	2.6
Temporal cortex	tissue	2.4
Motor cortex	tissue	2.3
Hippocampal formation	tissue	2.2
Rectum	tissue	2.0	high
Retrosplenial and cingulate cortex	tissue	2.0
Septum	tissue	2.0
Smooth muscle	tissue	1.9	not detected
Olfactory bulb	tissue	1.9
Retrosplenial cortex	tissue	1.9
Amygdala	tissue	1.8
Entorhinal cortex	tissue	1.8
Prefrontal cortex	tissue	1.5
Retina	tissue	1.4
Seminal vesicle	tissue	1.4	not detected
Occipital cortex	tissue	1.4
Putamen	tissue	1.2
Cerebellum	tissue	1.2	not detected
Insular cortex	tissue	1.2
Adipose tissue	tissue	1.0
Corpus callosum	tissue	1.0
Frontal cortex	tissue	0.9
Cervix	tissue	0.8	not detected
Pancreas	tissue	0.8	not detected
Nucleus accumbens	tissue	0.8
Stomach 1	tissue	0.7	not detected
Choroid plexus	tissue	0.6
Spleen	tissue	0.6	not detected
Hippocampus	tissue	0.6	not detected
Esophagus	tissue	0.5	not detected
Endometrium 1	tissue	0.5	not detected
Basal ganglia	tissue	0.5	not detected
Gallbladder	tissue	0.5	not detected
Skeletal muscle	tissue	0.4	not detected
Lung	tissue	0.3	not detected
Prostate	tissue	0.3	not detected
Caudate putamen	tissue	0.3
Lymph node	tissue	0.2	not detected
Ovary	tissue	0.2	not detected
Salivary gland	tissue	0.2	not detected

Brain sub-regions (HPA Brain Atlas): detected in 182; highest nTPM — Ventral spinal cord (346.7), Spinal trigeminal nucleus, oral (105.4), Spinal trigeminal nucleus, interpolar (100.9), Dorsal spinal cord (85.0), Parvicellular reticular nuclei, medullary (83.1).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SP1, TFAP2A

miRNA regulators (miRDB)

Targeting PRPH by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

24 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-370-5P	99.78	66.81	706
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-6513-3P	99.59	69.77	1102
HSA-MIR-4643	99.49	67.63	1791
HSA-MIR-642A-3P	99.23	67.67	1258
HSA-MIR-642B-3P	99.23	67.67	1258
HSA-MIR-6815-3P	99.13	68.98	1530
HSA-MIR-8066	99.05	68.66	1532
HSA-MIR-2467-3P	98.65	67.18	1969
HSA-MIR-4436B-3P	98.25	65.26	1494
HSA-MIR-6735-5P	98.24	65.36	1488
HSA-MIR-7843-5P	98.12	65.26	1421
HSA-MIR-506-5P	98.02	67.41	1065
HSA-MIR-4632-5P	97.82	65.38	1470
HSA-MIR-6879-5P	97.77	65.52	1521
HSA-MIR-3652	97.71	65.43	1890
HSA-MIR-4430	97.47	65.61	1813
HSA-MIR-3187-3P	97.38	65.80	904
HSA-MIR-5192	96.89	63.35	879
HSA-MIR-2355-3P	96.84	68.54	909

Functional genomics

gnomAD constraint: pLI 1.71e-15, LOEUF 1.16, missense Z 0.805 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000257860 — one region, missense o/e 0.91.

Literature-anchored findings (GeneRIF, showing 18)

• The data of this experiment document the expression of peripherin in Lewy body-like inclusions , which may provide a clue to the pathogenesis of neurodegeneration in ALS. (PMID:14675609)
• Peripherin overexpression in transgenic mice can cause defective transport of type IV neurofilament proteins, a phenomenon that may account for the progressive formation of amyotrophic lateral sclerosis-like spheroids in axons. (PMID:16787413)
• peripherin is a novel substrate for Akt in vivo and its phosphorylation may play a role in motor nerve regeneration (PMID:17569669)
• Peripherin splicing abnormalities occur in amyotrophic lateral sclerosis generating aggregation-prone splice isoforms, one of which causes peripherin aggregation when its expression is upregulated. (PMID:18287500)
• PKCepsilon through its interaction with peripherin facilitates its aggregation and subsequent cell death (PMID:18408015)
• Expression of the 2 markers, peripherin and alpha-internexin, in a small round cell tumor strongly favors the diagnosis of neuroblastoma. (PMID:18528283)
• Transgenic mice expressing the PRPH-EGFP genomic reporter display intrinsic peripheral nervous system fluorescence. (PMID:18709437)
• This work contributes to determine the role of PRPH gene variants in ALS. Further studies are necessary to define the mechanisms through which the mutant peripherin could cause ALS phenotype. (PMID:20363051)
• Transgenic peripherin isoform expression reveals post-transcriptional changes to the normal expression pattern associated with malformed filaments and intracellular inclusions underlying a role in the pathogenesis of amyotrophic lateral sclerosis. (PMID:20533992)
• study analyzed expression of peripherin(PP) in the cochlea; in organ of Corti, PP seems to be specifically expressed in outer hair cell afferents; small or type II spiral ganglion cell bodies also intensely express PP (PMID:21088854)
• although the mechanisms underlying peripherin co-localization in Bunina bodies are unknown, peripherin could be involved in forming these inclusions (PMID:21241994)
• A protein encoded by this locus was found to be differentially expressed in postmortem brains from patients with atypical frontotemporal lobar degeneration. (PMID:22360420)
• interaction between disease-causing RAB7A mutants and peripherin could play an important role in Charcot-Marie-Tooth type 2B neuropathy (PMID:23179371)
• In patients with HD, a panel using calretinin and peripherin with or without MAP-2 may be most helpful in identifying transition zones (PMID:26469323)
• To discover of Phosphorylated autoantigens Peripherin as a Major Humoral Autoantigen in Type 1 Diabetes Mellitus. (PMID:27185639)
• Desmin, Glial Fibrillary Acidic Protein, Vimentin, and Peripherin are type III intermediate filaments that have roles in health and disease [review] (PMID:29196434)
• Mutation in the peripherin gene is associated cone-rod dysfunction or dominant maculopathy. (PMID:30822235)
• Genome-wide association study of sural nerve conduction amplitude and velocity in 7045 Icelanders and find a low-frequency splice-donor variant in PRPH associated with reduced amplitude of the sural nerve action potential, but not with sural nerve conduction velocity. (PMID:30992453)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	prph	ENSDARG00000028306
mus_musculus	Prph	ENSMUSG00000023484
rattus_norvegicus	Prph	ENSRNOG00000052880

Paralogs (68): KRT33A (ENSG00000006059), VIM (ENSG00000026025), KRT31 (ENSG00000094796), NEFM (ENSG00000104722), KRT23 (ENSG00000108244), KRT37 (ENSG00000108417), KRT32 (ENSG00000108759), KRT18 (ENSG00000111057), LMNB1 (ENSG00000113368), KRT36 (ENSG00000126337), KRT17 (ENSG00000128422), GFAP (ENSG00000131095), KRT34 (ENSG00000131737), KRT33B (ENSG00000131738), NES (ENSG00000132688), KRT85 (ENSG00000135443), KRT7 (ENSG00000135480), KRT71 (ENSG00000139648), INA (ENSG00000148798), LMNTD1 (ENSG00000152936), LMNA (ENSG00000160789), KRT84 (ENSG00000161849), KRT82 (ENSG00000161850), KRT80 (ENSG00000167767), KRT1 (ENSG00000167768), KRT24 (ENSG00000167916), KRT8 (ENSG00000170421), KRT78 (ENSG00000170423), KRT86 (ENSG00000170442), KRT75 (ENSG00000170454), KRT6C (ENSG00000170465), KRT4 (ENSG00000170477), KRT74 (ENSG00000170484), KRT72 (ENSG00000170486), KRT83 (ENSG00000170523), BFSP2 (ENSG00000170819), KRT19 (ENSG00000171345), KRT15 (ENSG00000171346), KRT38 (ENSG00000171360), KRT13 (ENSG00000171401), KRT9 (ENSG00000171403), KRT20 (ENSG00000171431), KRT27 (ENSG00000171446), KRT2 (ENSG00000172867), KRT28 (ENSG00000173908), DES (ENSG00000175084), LMNB2 (ENSG00000176619), SYNM (ENSG00000182253), KRT76 (ENSG00000185069), KRT6B (ENSG00000185479), KRT79 (ENSG00000185640), KRT73 (ENSG00000186049), KRT5 (ENSG00000186081), KRT26 (ENSG00000186393), KRT10 (ENSG00000186395), KRT3 (ENSG00000186442), KRT16 (ENSG00000186832), KRT14 (ENSG00000186847), KRT12 (ENSG00000187242), KRT77 (ENSG00000189182)

+8 more (showing top 60).

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:97774) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 2 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal sensory neuron morphology	1
abnormal axon morphology	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Chlorocebus aethiops	P84198	100.0%	Diamond
Macaca fascicularis	Q4R4X4	100.0%	Diamond
Pongo abelii	Q5R408	100.0%	Diamond
Bos taurus	P48616	99.4%	Diamond
Ovis aries	Q9MZA9	99.4%	Diamond
Mesocricetus auratus	P02544	99.3%	Diamond
Cricetulus griseus	P48670	99.3%	Diamond
Sus scrofa	P02547	98.2%	Diamond
Pan troglodytes	Q5R1W8	97.9%	Diamond
Canis lupus familiaris	A0A8C0N8E3	97.4%	Diamond
Carassius auratus	P48677	95.6%	Diamond
Acanthocheilonema viteae	Q17107	93.4%	Diamond
Xenopus laevis	P24789	92.4%	Diamond
Gallus gallus	P09654	86.7%	Diamond
Oryctolagus cuniculus	P54938	86.1%	Diamond
Ascaris suum	P23730	80.5%	Diamond
Xenopus tropicalis	B4F721	80.2%	Diamond
Cyprinus carpio	Q92155	79.6%	Diamond
Coturnix japonica	Q02916	77.8%	Diamond
Oncorhynchus mykiss	P48674	76.3%	Diamond
Tetronarce californica	P23729	60.1%	Diamond
Branchiostoma lanceolatum	Q04948	41.4%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
TROAP-AS1	ncRNA	101927267
C1QL4	protein-coding	338761
DNAJC22	protein-coding	79962
TUBA1C	protein-coding	84790
TROAP	protein-coding	10024
TUBA1A	protein-coding	7846
TUBA1B-AS1	ncRNA	105369760
TUBA1B	protein-coding	10376
SPATS2	protein-coding	65244

Protein

Protein identifiers

Peripherin — P41219 (reviewed: P41219)

Alternative names: Neurofilament 4

All UniProt accessions (3): P41219, F8W835, H7C5W5

UniProt curated annotations — full annotation on UniProt →

Function. Class-III neuronal intermediate filament protein. May form an independent structural network without the involvement of other neurofilaments or may cooperate with the neuronal intermediate filament proteins NEFL, NEFH, NEFM and INA to form a filamentous network. Assembly of the neuronal intermediate filaments may be regulated by RAB7A. Plays a role in the development of unmyelinated sensory neurons. May be involved in axon elongation and axon regeneration after injury. Inhibits neurite extension in type II spiral ganglion neurons in the cochlea.

Subunit / interactions. Forms homodimers (in vitro). Homopolymerizes into a filamentous network (in vitro). Forms heterodimers with NEFL, NEFM or NEFH (in vitro). Interacts with DST (via C-terminus). Interacts with RAB7A; the interaction is direct. Interacts with PRKCE (via phorbol-ester/DAG-type 2 domain).

Subcellular location. Cytoplasm. Cytoskeleton. Cell projection. Axon. Perikaryon.

Tissue specificity. Expressed in the neurons of the outer hair cells in the organ of Corti and to a lesser extent in type I spiral ganglion cells.

Post-translational modifications. Phosphorylated; phosphorylation increases after nerve injury in regenerating neurons.

Disease relevance. Amyotrophic lateral sclerosis (ALS) [MIM:105400] A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. Disease susceptibility may be associated with variants affecting the gene represented in this entry.

Miscellaneous. Gene prediction based on similarity to orthologs.

Similarity. Belongs to the intermediate filament family.

Isoforms (2)

UniProt ID	Names	Canonical?
P41219-1	1	yes
P41219-2	2

RefSeq proteins (1): NP_006253* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002957	Keratin_I	Family
IPR006821	Intermed_filament_DNA-bd	Domain
IPR018039	IF_conserved	Conserved_site
IPR039008	IF_rod_dom	Domain
IPR050405	Intermediate_filament	Family

Pfam: PF00038, PF04732

UniProt features (21 total): region of interest 8, modified residue 6, sequence variant 2, chain 1, domain 1, compositionally biased region 1, splice variant 1, sequence conflict 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P41219-F1	79.24	0.56

Human Protein Atlas

Protein class: Predicted intracellular proteins, Disease related genes, Human disease related genes

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH enhanced

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 (6)

Type	Positions
3’-nitrotyrosine	17, 379
Phosphoserine	28, 50, 59
Phosphotyrosine	470

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 223 (showing top): MORF_RAGE, GOBP_INTERMEDIATE_FILAMENT_BASED_PROCESS, GOBP_INTERMEDIATE_FILAMENT_ORGANIZATION, LUCAS_HNF4A_TARGETS_UP, GGGTGGRR_PAX4_03, CAR_MYST2, SCHAEFFER_PROSTATE_DEVELOPMENT_12HR_DN, SCHLOSSER_SERUM_RESPONSE_DN, HELLER_HDAC_TARGETS_SILENCED_BY_METHYLATION_UP, CAR_MLANA, MORF_PML, GOCC_NEURON_PROJECTION, MORF_PDPK1, MORF_IKBKG, CTGYNNCTYTAA_UNKNOWN

GO Biological Process (1): intermediate filament organization (GO:0045109)

GO Molecular Function (3): structural molecule activity (GO:0005198), structural constituent of cytoskeleton (GO:0005200), protein binding (GO:0005515)

GO Cellular Component (9): intermediate filament (GO:0005882), plasma membrane (GO:0005886), membrane (GO:0016020), axon (GO:0030424), perikaryon (GO:0043204), type III intermediate filament (GO:0045098), extracellular exosome (GO:0070062), cytoskeleton (GO:0005856), intermediate filament cytoskeleton (GO:0045111)

GO top-level categories

17 GO namespaces:

Category	Terms
cytoskeleton	2
cellular anatomical structure	2
intermediate filament cytoskeleton organization	1
supramolecular fiber organization	1
molecular_function	1
structural molecule activity	1
cytoskeleton organization	1
binding	1
intermediate filament cytoskeleton	1
polymeric cytoskeletal fiber	1
membrane	1
cell periphery	1
neuron projection	1
neuronal cell body	1
intermediate filament	1
extracellular vesicle	1
intracellular membraneless organelle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 2 of 13 annotations. The rest are phylogenetic / computational / electronic (IEA).

2 experimentally-supported GO terms:

GO term	NS	Evidence
extracellular exosome	CC	high-throughput assay
membrane	CC	high-throughput assay

Protein interactions and networks

STRING

showing 15 of 294 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRPH	PDE6G	P18545	296
PRPH	PARP16	Q8N5Y8	296
PRPH	PARP4	Q9UKK3	296
PRPH	TPST2	O60704	260
PRPH	TIPARP	Q7Z3E1	256
PRPH	PLK5	Q496M5	241
PRPH	MAFF	Q9ULX9	235
PRPH	LYPD1	Q8N2G4	232
PRPH	PRPH2	P23942	223
PRPH	ETV4	P43268	214
PRPH	LYPLA2	O95372	213
PRPH	RHPN2	Q8IUC4	212
PRPH	KRTDAP	P60985	206
PRPH	PENK	P01210	204
PRPH	BHLHE22	Q8NFJ8	204

IntAct

Human interaction partners of PRPH in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 75 partners by confidence:

Partner	Interaction type	MIscore	Records
DES	physical association	0.780	6
KRT19	physical association	0.720	6
KRT20	physical association	0.720	6
LNX1	physical association	0.720	6
TCP10L	physical association	0.720	6
VIM	physical association	0.670	4
FAM167A	physical association	0.670	3
ARNT2	physical association	0.560	3
ATL1	physical association	0.560	3
BRK1	physical association	0.560	3
CCDC120	physical association	0.560	3
CDC37	physical association	0.560	3
CENPV	physical association	0.560	3
COPS3	physical association	0.560	3
CRYAA	physical association	0.560	3
CT55	physical association	0.560	3
DDX6	physical association	0.560	3
ENKUR	physical association	0.560	3
FCHO1	physical association	0.560	3
HAUS7	physical association	0.560	3
IFT20	physical association	0.560	3
INCA1	physical association	0.560	3
KCTD17	physical association	0.560	3
KIAA0408	physical association	0.560	3
KIAA1217	physical association	0.560	3
KIFC3	physical association	0.560	3
KLC3	physical association	0.560	3
KRT14	physical association	0.560	3
KRT16	physical association	0.560	3
KRT24	physical association	0.560	3

BioGRID (225 interactions; top human partners by supporting records): VIM (Two-hybrid; 5 records), KRT19 (Two-hybrid; 3 records), KRT8 (Proximity Label-MS; 3 records), DES (Two-hybrid; 2 records), FAM167A (Affinity Capture-MS; 2 records), GAN (Affinity Capture-MS; 2 records), KIF14 (Affinity Capture-MS; 2 records), KRT14 (Two-hybrid; 2 records), KRT15 (Two-hybrid; 2 records), KRT16 (Two-hybrid; 2 records), KRT18 (Proximity Label-MS; 2 records), KRT75 (Two-hybrid; 2 records), LNX1 (Two-hybrid; 2 records), NES (Proximity Label-MS; 2 records), PPP1R13B (Two-hybrid; 2 records)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
AKT	“up-regulates activity”	PRPH	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 75 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
Formation of the cornified envelope	10	21.4×	7e-09
Keratinization	10	13.6×	3e-07

GO biological processes:

GO term	Partners	Fold	FDR
morphogenesis of an epithelium	9	46.2×	5e-11
intermediate filament organization	12	43.1×	2e-14
epithelial cell differentiation	7	18.3×	1e-05

Disease & clinical

Genetic variants

Variant evidence for PRPH: 95 ClinVar records (2 pathogenic / likely pathogenic); 2 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	2
Uncertain significance	67
Likely benign	3
Benign	9

Top pathogenic / likely-pathogenic (2)

Showing all 2 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
3234975	NM_006262.4(PRPH):c.919C>T (p.Gln307Ter)	Likely pathogenic	criteria provided, single submitter	1
4845223	NM_006262.4(PRPH):c.745C>T (p.Gln249Ter)	Likely pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore PRPH’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 22 predictions of 630):

Position(s)	Effect	Δscore	Sites
12:49296172	acceptor_gain	1.0000
12:49296176–49296177	acceptor_loss	1.0000	5
12:49296239–49296240	donor_loss	1.0000	4
12:49296417	acceptor_gain	1.0000
12:49296427	acceptor_gain	1.0000
12:49296820	acceptor_gain	1.0000
12:49296831	acceptor_gain	1.0000
12:49297057	donor_loss	1.0000	2
12:49297140	acceptor_gain	1.0000
12:49297274–49297275	donor_loss	1.0000	5

AlphaMissense

1,178 missense substitutions predicted likely pathogenic (of 3,041 scored), across 316 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M372	9	0.912	0.977
N105	8	0.996	0.999
D390	8	0.996	0.999
F108	8	0.991	1.000
D205	8	0.986	0.995
N122	8	0.978	0.994
F227	8	0.954	0.999
N279	8	0.945	0.990
D203	8	0.930	0.973
D106	8	0.897	0.964
D293	8	0.872	0.943
H375	8	0.846	0.985
H232	8	0.842	0.987
D223	8	0.790	0.943
E392	7	0.998	1.000
F111	7	0.994	0.998
I393	7	0.991	1.000
E403	7	0.982	0.993
M387	7	0.975	0.996
E97	7	0.971	0.996

HPA cancer prognostics

RNA cancer specificity: Group enriched (Glioblastoma Multiforme, Pancreatic Adenocarcinoma, Testicular Germ Cell Tumor, Uterine Corpus Endometrial Carcinoma)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Glioblastoma Multiforme (TCGA)	unfavorable	2.25e-05

Disease associations

OMIM: gene MIM:170710 | disease phenotypes: MIM:105400

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
amyotrophic lateral sclerosis type 1	Moderate	Autosomal dominant	3
amyotrophic lateral sclerosis	Limited	Autosomal dominant

ClinGen Gene-Disease Validity

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

1 validity classifications:

Disease	Classification	Inheritance
amyotrophic lateral sclerosis	Limited	AD

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (2 panels, 0 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

2 panels:

Panel	Rating
Adult-onset neurological disorders	amber
Neurodegenerative disorders, adult onset	amber

Mondo (2): amyotrophic lateral sclerosis type 1 (MONDO:0007103), amyotrophic lateral sclerosis (MONDO:0004976)

Orphanet (1): Amyotrophic lateral sclerosis (Orphanet:803)

HPO phenotypes

55 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000217	Xerostomia
HP:0000708	Atypical behavior
HP:0000712	Emotional lability
HP:0000716	Depression
HP:0000739	Anxiety
HP:0001257	Spasticity
HP:0001260	Dysarthria
HP:0001308	Tongue fasciculations
HP:0001324	Muscle weakness
HP:0001347	Hyperreflexia
HP:0001618	Dysphonia
HP:0001824	Weight loss
HP:0002015	Dysphagia
HP:0002094	Dyspnea
HP:0002145	Frontotemporal dementia
HP:0002180	Neurodegeneration
HP:0002307	Drooling
HP:0002313	Spastic paraparesis
HP:0002314	Degeneration of the lateral corticospinal tracts
HP:0002360	Sleep disturbance
HP:0002380	Fasciculations
HP:0002398	Degeneration of anterior horn cells
HP:0002463	Language impairment
HP:0002878	Respiratory failure
HP:0003202	Skeletal muscle atrophy
HP:0003324	Generalized muscle weakness
HP:0003376	Steppage gait
HP:0003394	Muscle spasm
HP:0003470	Paralysis
HP:0003484	Upper limb muscle weakness
HP:0003487	Babinski sign
HP:0003581	Adult onset
HP:0003693	Distal amyotrophy
HP:0004326	Cachexia
HP:0007024	Pseudobulbar paralysis
HP:0007340	Lower limb muscle weakness
HP:0007354	Amyotrophic lateral sclerosis
HP:0007373	Motor neuron atrophy
HP:0008955	Progressive distal muscular atrophy
HP:0009027	Foot dorsiflexor weakness
HP:0010535	Sleep apnea
HP:0012378	Fatigue
HP:0012473	Tongue atrophy
HP:0012531	Pain
HP:0012764	Orthopnea
HP:0025425	Laryngospasm
HP:0030192	Fatigable weakness of bulbar muscles
HP:0030195	Fatigable weakness of swallowing muscles
HP:0030196	Fatigable weakness of respiratory muscles
HP:0030878	Abnormality on pulmonary function testing
HP:0031993	Hoffmann sign
HP:0033683	Jaw hyperreflexia
HP:0100543	Cognitive impairment

GWAS associations

2 associations:

Study	Trait	p-value
GCST001148_9	Prostate cancer	7e-12
GCST008312_1	Sural nerve amplitude potential	1e-11

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0010070	nerve conduction amplitude

MeSH disease descriptors

2 disease descriptors:

Descriptor	Name	Tree numbers
D000690	Amyotrophic Lateral Sclerosis	C10.228.854.139; C10.574.562.250; C10.574.950.050; C10.668.467.250; C18.452.845.800.050
C531617	Amyotrophic lateral sclerosis 1 *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066904 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (2 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.39	Kd	40.97	nM	CHEMBL3752910
6.75	ED50	178.3	nM	CHEMBL3752910
6.40	Kd	399.6	nM	CHEMBL5653589
5.76	ED50	1739	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 4 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149094: Binding affinity to human PRPH incubated for 45 mins by Kinobead based pull down assay	kd	0.0410	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149094: Binding affinity to human PRPH incubated for 45 mins by Kinobead based pull down assay	kd	0.3996	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression	4
sodium arsenite	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
propionaldehyde	increases expression	1
bisphenol A	decreases expression	1
sodium arsenate	decreases expression, increases abundance	1
arsenite	increases methylation	1
sulforaphane	affects binding	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	increases expression	1
ferrous chloride	decreases expression	1
pentanal	increases expression	1
monomethylarsonous acid	increases expression	1
jinfukang	increases expression	1
NSC 689534	affects binding, increases expression	1
Temozolomide	increases expression	1
Decitabine	affects expression	1
Sunitinib	increases expression	1
Aldehydes	increases expression	1
Arsenic	decreases expression, increases abundance	1
Atrazine	increases expression	1
Caffeine	decreases expression	1
Cannabidiol	increases expression	1
Cisplatin	affects expression	1
Copper	affects binding, increases expression	1
Cytarabine	decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
Dimethyl Sulfoxide	affects expression	1
Ivermectin	decreases expression	1
Silicon Dioxide	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652136	Binding	Binding affinity to human PRPH incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — *ChemMedChem*

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 299 trials:

NCT	Phase	Status	Title
NCT00542412	Phase 4	COMPLETED	CARE Canadian ALS Riluzole Evaluation
NCT00560287	Phase 4	UNKNOWN	Non-Invasive Ventilation in Amyotrophic Lateral Sclerosis
NCT00613899	Phase 4	COMPLETED	Feasibility of Telesurveillance and Home Cough Assistance for Amyotrophic Lateral Patients (ALS)
NCT04997954	Phase 4	UNKNOWN	EMERALD TRIAL Open Label Extension Study
NCT06849115	Phase 4	COMPLETED	Effects of L-Carnitine in Amyotrophic Lateral Sclerosis Patients With CHCHD10 Mutations
NCT07223723	Phase 4	ACTIVE_NOT_RECRUITING	A Study to Learn More About the Long-Term Safety of Tofersen (Qalsody) in Chinese Participants With SOD-1 Amyotrophic Lateral Sclerosis (ALS)
NCT00021697	Phase 3	COMPLETED	Safety/Efficacy of AVP-923 in the Treatment of Emotional Lability (Uncontrolled Crying & Laughing) in Patients With ALS
NCT00035815	Phase 3	COMPLETED	Insulin-like Growth Factor-1 in Amyotrophic Lateral Sclerosis (ALS) Trial
NCT00047723	Phase 3	COMPLETED	Minocycline to Treat Amyotrophic Lateral Sclerosis
NCT00069186	Phase 3	UNKNOWN	Study of Creatine Monohydrate in Patients With Amyotrophic Lateral Sclerosis
NCT00136110	Phase 3	COMPLETED	Trial of Sodium Valproate in Amyotrophic Lateral Sclerosis
NCT00330681	Phase 3	COMPLETED	Efficacy and Safety Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis (ALS)
NCT00349622	Phase 3	COMPLETED	Clinical Trial Ceftriaxone in Subjects With ALS
NCT00372879	Phase 3	COMPLETED	Clinical Trial of Vitamin E to Treat Muscular Cramps in Patients With ALS
NCT00415519	Phase 3	COMPLETED	Efficacy and Safety Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis (ALS) Who Met Severity Classification III
NCT00424463	Phase 3	COMPLETED	Expanded Controlled Study of Safety and Efficacy of MCI-186 in Patients With Amyotrophic Lateral Sclerosis (ALS)
NCT00839033	Phase 3	TERMINATED	Evaluation of a Mechanical Device During Acute Respiratory Failure in Patients With Neuromuscular Disorders
NCT00868166	Phase 3	COMPLETED	Safety and Efficacy of TRO19622 as add-on Therapy to Riluzole Versus Placebo in Treatment of Patients Suffering From ALS
NCT00965497	Phase 3	COMPLETED	Escitalopram (Lexapro) for Depression MS or ALS
NCT01016522	Phase 3	TERMINATED	Safety and Tolerability of the Ketogenic Diet in Amyotrophic Lateral Sclerosis (ALS)
NCT01160263	Phase 3	COMPLETED	Study of Dopamine and Serotonin Transporters in Patients With Amyotrophic Lateral Sclerosis and Controls
NCT01281189	Phase 3	COMPLETED	Phase 3 Study of Dexpramipexole in ALS
NCT01492686	Phase 3	COMPLETED	Phase 3 Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis
NCT01583088	Phase 3	TERMINATED	Early Stage Amyotrophic Lateral Sclerosis Phrenic Stimulation
NCT01622088	Phase 3	TERMINATED	Phase 3 Extension Study of Dexpramipexole in ALS
NCT02496767	Phase 3	COMPLETED	Ventilatory Investigation of Tirasemtiv and Assessment of Longitudinal Indices After Treatment for a Year
NCT02623699	Phase 3	COMPLETED	An Efficacy, Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of BIIB067 (Tofersen) in Adults With Inherited Amyotrophic Lateral Sclerosis (ALS)
NCT02936635	Phase 3	COMPLETED	A Study for Patients Who Completed VITALITY-ALS (CY 4031)
NCT03127267	Phase 3	RECRUITING	Efficacy and Safety of Masitinib Versus Placebo in the Treatment of ALS Patients
NCT03280056	Phase 3	COMPLETED	Safety and Efficacy of Repeated Administrations of NurOwn® in ALS Patients
NCT03491462	Phase 3	COMPLETED	Arimoclomol in Amyotropic Lateral Sclerosis
NCT03505021	Phase 3	COMPLETED	Effects of Oral Levosimendan (ODM-109) on Respiratory Function in Patients With ALS
NCT03548311	Phase 3	COMPLETED	Clinical Trial of Ultra-high Dose Methylcobalamin for ALS
NCT03690791	Phase 3	UNKNOWN	Efficacy of Cannabinoids in Amyotrophic Lateral Sclerosis or Motor Neurone Disease
NCT03800524	Phase 3	UNKNOWN	Safety and Efficacy of TUDCA as add-on Treatment in Patients Affected by ALS
NCT03836716	Phase 3	TERMINATED	Arimoclomol in Amyotropic Lateral Sclerosis - Open Label Extension Trial
NCT03948178	Phase 3	TERMINATED	Effects of Oral Levosimendan on Respiratory Function in Patients With Amyotrophic Lateral Sclerosis (ALS): Open-Label Extension
NCT04165824	Phase 3	COMPLETED	Safety Study of Oral Edaravone Administered in Subjects With ALS
NCT04248465	Phase 3	TERMINATED	An Efficacy and Safety Study of Ravulizumab in ALS Participants
NCT04569084	Phase 3	TERMINATED	Efficacy and Safety Study of Oral Edaravone Administered in Subjects With ALS
NCT04577404	Phase 3	COMPLETED	Safety Extension Study of Oral Edaravone Administered in Subjects With Amyotrophic Lateral Sclerosis (ALS)
NCT04745299	Phase 3	COMPLETED	Evaluation the Efficacy and Safety of Mutiple Lenzumestrocel (Neuronata-R® Inj.) Treatment in Patients With ALS
NCT04768972	Phase 3	ACTIVE_NOT_RECRUITING	FUSION: A Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of ION363 in Amyotrophic Lateral Sclerosis Participants With Fused in Sarcoma Mutations (FUS-ALS)
NCT04944784	Phase 3	TERMINATED	A Study to Evaluate the Efficacy and Safety of Reldesemtiv in Patients With Amyotrophic Lateral Sclerosis (ALS)
NCT05021536	Phase 3	UNKNOWN	Phase III Trial of AMX0035 for Amyotrophic Lateral Sclerosis Treatment
NCT05151471	Phase 3	TERMINATED	Efficacy and Safety Extension Study of Oral Edaravone Administered in Subjects With ALS
NCT05178810	Phase 3	COMPLETED	Study to Investigate the Efficacy and Safety of FAB122 (Daily Oral Edaravone) in Patients With Amyotrophic Lateral Sclerosis
NCT05193994	Phase 3	TERMINATED	Triumeq in Amyotrophic Lateral Sclerosis
NCT05442775	Phase 3	TERMINATED	A Phase 3, Open-Label Extension of COURAGE-ALS (CY 5031)
NCT05568615	Phase 3	COMPLETED	Extension Study Following the Studies MT-1186-A03 or A04 to Evaluate the Safety of Oral Edaravone in Subjects With ALS
NCT05619783	Phase 3	COMPLETED	Extension Study Evaluating The Safety And Tolerability of AMX0035
NCT05753852	Phase 3	UNKNOWN	Open Label Extension of TUDCA-ALS Study
NCT05866926	Phase 3	TERMINATED	Study to Investigate the Long-term Safety of FAB122 in Patients With Amyotrophic Lateral Sclerosis
NCT06008249	Phase 3	TERMINATED	Platform Trial to Assess the Efficacy of Multiple Drugs in Amyotrophic Lateral Sclerosis (ALS)
NCT06658977	Phase 3	TERMINATED	RolloverTreatment With Triumeq for People With ALS Following the Lighthouse II Trial
NCT06973629	Phase 3	NOT_YET_RECRUITING	Efficacy and Safety of MSC-NTF (NurOwn) in Participants With Early Symptomatic ALS and Moderate Disease Presentation in ALS (ENDURANCE STUDY)
NCT07174492	Phase 3	NOT_YET_RECRUITING	Efficacy and Safety of Masitinib in Combination With SoC Versus Placebo in the Treatment of ALS Patients
NCT07322003	Phase 3	RECRUITING	Pridopidine Phase 3 Study to Evaluate Efficacy and Safety in ALS
NCT03204500	Phase 2	COMPLETED	Dual Treatment With Lithium and Valproate in ALS.
NCT00004771	Phase 2	COMPLETED	Phase II Study of Leuprolide and Testosterone for Men With Kennedy’s Disease or Other Motor Neuron Disease

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for PRPH across ~30M SureChEMBL compounds — explore on Sugi Predict.