RNF170

Summary

RNF170 (ring finger protein 170, HGNC:25358) is a protein-coding gene on chromosome 8p11.21, encoding E3 ubiquitin-protein ligase RNF170 (Q96K19). E3 ubiquitin-protein ligase that plays an essential role in stimulus-induced inositol 1,4,5-trisphosphate receptor type 1 (ITPR1) ubiquitination and degradation via the endoplasmic reticulum-associated degradation (ERAD) pathway.

This gene encodes a RING domain-containing protein that resides in the endoplasmic reticulum (ER) membrane. This protein functions as an E3 ubiquitin ligase and mediates ubiquitination and processing of inositol 1,4,5-trisphosphate (IP3) receptors via the ER-associated protein degradation pathway. It is recruited to the activated IP3 receptors by the ERLIN1/ERLIN2 complex to which it is constitutively bound. Mutations in this gene are associated with autosomal dominant sensory ataxia. Alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 81790 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal dominant sensory ataxia 1 (Strong, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 63 total — 4 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 39
• MANE Select transcript: NM_030954

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25358
Approved symbol	RNF170
Name	ring finger protein 170
Location	8p11.21
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP564A022, ADSA
Ensembl gene	ENSG00000120925
Ensembl biotype	protein_coding
OMIM	614649
Entrez	81790

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 23 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000240159, ENST00000319073, ENST00000319104, ENST00000524954, ENST00000526349, ENST00000527424, ENST00000528318, ENST00000531440, ENST00000534961, ENST00000862753, ENST00000862754, ENST00000862755, ENST00000862756, ENST00000862757, ENST00000862758, ENST00000862759, ENST00000862760, ENST00000862761, ENST00000862762, ENST00000862763, ENST00000913384, ENST00000969232, ENST00000969233, ENST00000969234, ENST00000969235

RefSeq mRNA: 4 — MANE Select: NM_030954 NM_001160223, NM_001160224, NM_001160225, NM_030954

CCDS: CCDS55229, CCDS55230, CCDS6138

Canonical transcript exons

ENST00000527424 — 7 exons

Exon	Start	End
ENSE00002163020	42896484	42896605
ENSE00002184629	42853301	42856428
ENSE00003567977	42887728	42887871
ENSE00003614933	42861745	42861855
ENSE00003643269	42873931	42874006
ENSE00003678305	42865416	42865489
ENSE00003714369	42870004	42870112

Expression profiles

Bgee: expression breadth ubiquitous, 281 present calls, max score 91.79.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.5736 / max 100.4753, expressed in 1785 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
92936	4.9284	1677
92937	2.9607	1424
92938	1.6845	1051

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lateral nuclear group of thalamus	UBERON:0002736	91.79	gold quality
tendon of biceps brachii	UBERON:0008188	91.74	gold quality
adrenal tissue	UBERON:0018303	91.41	gold quality
secondary oocyte	CL:0000655	91.08	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.62	gold quality
substantia nigra pars compacta	UBERON:0001965	90.19	gold quality
oocyte	CL:0000023	89.90	gold quality
pons	UBERON:0000988	89.77	gold quality
substantia nigra pars reticulata	UBERON:0001966	89.50	gold quality
upper leg skin	UBERON:0004262	89.05	gold quality
subthalamic nucleus	UBERON:0001906	88.67	gold quality
placenta	UBERON:0001987	88.60	gold quality
superior vestibular nucleus	UBERON:0007227	88.54	gold quality
corpus epididymis	UBERON:0004359	88.19	gold quality
inferior vagus X ganglion	UBERON:0005363	88.13	gold quality
skin of hip	UBERON:0001554	87.84	gold quality
corpus callosum	UBERON:0002336	87.77	gold quality
thyroid gland	UBERON:0002046	87.60	gold quality
tendon	UBERON:0000043	87.37	gold quality
globus pallidus	UBERON:0001875	87.30	gold quality
medial globus pallidus	UBERON:0002477	87.30	gold quality
right lobe of thyroid gland	UBERON:0001119	87.26	gold quality
left lobe of thyroid gland	UBERON:0001120	87.24	gold quality
calcaneal tendon	UBERON:0003701	86.51	gold quality
lateral globus pallidus	UBERON:0002476	86.48	gold quality
bronchial epithelial cell	CL:0002328	86.47	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	86.38	gold quality
ventral tegmental area	UBERON:0002691	86.28	gold quality
dorsal plus ventral thalamus	UBERON:0001897	86.11	gold quality
spinal cord	UBERON:0002240	86.00	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.40

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

99 targeting RNF170, 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-4668-3P	100.00	68.74	2635
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-3529-3P	99.90	73.55	3045

Literature-anchored findings (GeneRIF, showing 6)

• Together these results suggest that the mutation in RNF170 is causal for the sensory ataxia (PMID:21115467)
• RNF170 plays an essential role in IP(3) receptor processing via the ubiquitin-proteasome pathway. (PMID:21610068)
• aberrant ubiquitination of substrates, or cellular adaptation to chronically reduced RNF170 levels likely accounts for the autosomal dominant sensory ataxia-associated Ca2+ signaling deficit (PMID:25882839)
• mutations in the ubiquitin E3 ligase gene RNF170, which targets inositol 1,4,5-trisphosphate receptors for degradation, are the likely cause of autosomal recessive HSP in four unrelated families and functionally evaluate the consequences of mutations in patient fibroblasts and mutant SH-SY5Y cells. Our findings highlight inositol 1,4,5-trisphosphate signaling as a candidate key pathway for hereditary spastic paraplegias. (PMID:31636353)
• RNF170-Related Hereditary Spastic Paraplegia: Confirmation by a Novel Mutation. (PMID:33165979)
• RNF170 mutation causes autosomal dominant sensory ataxia with variable pyramidal involvement. (PMID:34469621)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	rnf170	ENSDARG00000104069
mus_musculus	Rnf170	ENSMUSG00000013878
rattus_norvegicus	Rnf170	ENSRNOG00000069749
caenorhabditis_elegans		WBGENE00012606

Protein

Protein identifiers

E3 ubiquitin-protein ligase RNF170 — Q96K19 (reviewed: Q96K19)

Alternative names: Putative LAG1-interacting protein, RING finger protein 170, RING-type E3 ubiquitin transferase RNF170

All UniProt accessions (3): E9PNG8, E9PP55, Q96K19

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin-protein ligase that plays an essential role in stimulus-induced inositol 1,4,5-trisphosphate receptor type 1 (ITPR1) ubiquitination and degradation via the endoplasmic reticulum-associated degradation (ERAD) pathway. Also involved in ITPR1 turnover in resting cells. Selectively inhibits the TLR3-triggered innate immune response by promoting the ‘Lys-48’-linked polyubiquitination and degradation of TLR3.

Subunit / interactions. (Microbial infection) Interacts with human cytomegalovirus protein NEC2/UL50; this interaction promotes of UBA7 ubiquitination and subsequent proteasomal degradation. Constitutively associated with the ERLIN1/ERLIN 2 complex. Interacts with activated ITPR1.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Expressed in the spinal cord.

Disease relevance. Ataxia, sensory, 1, autosomal dominant (SNAX1) [MIM:608984] A rare disease characterized by progressive ataxia caused by degeneration of the posterior columns of the spinal cord. Affected individuals have a reduced ability to feel pain, temperature and vibration, particularly in the hands and feet. Their most prominent feature is an ataxic gait resulting from a severe loss of proprioception. Thus, patients rely on visual cues for maintaining proper body posture, such that they are unable to remain upright if their eyes are closed (Romberg sign). The disease is caused by variants affecting the gene represented in this entry. Spastic paraplegia 85, autosomal recessive (SPG85) [MIM:619686] A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG85 is an autosomal recessive form characterized by onset of motor symptoms in the first few years of life. Patients may have upper limb involvement and demonstrate axonal polyneuropathy. Additional features include optic atrophy, dysarthria, dysphagia, ataxia, and urinary incontinence. Brain imaging may show cerebellar atrophy. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Protein modification; protein ubiquitination.

Isoforms (6)

UniProt ID	Names	Canonical?
Q96K19-1	1	yes
Q96K19-2	2
Q96K19-3	3
Q96K19-4	4
Q96K19-5	5
Q96K19-6	6

RefSeq proteins (4): NP_001153695, NP_001153696, NP_001153697, NP_112216* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001841	Znf_RING	Domain
IPR010652	DUF1232	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR017907	Znf_RING_CS	Conserved_site
IPR027370	Znf-RING_euk	Domain
IPR038896	RNF170	Family

Pfam: PF06803, PF13445

UniProt features (26 total): splice variant 8, topological domain 4, sequence variant 4, transmembrane region 3, sequence conflict 3, mutagenesis site 2, chain 1, zinc finger region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96K19-F1	77.93	0.25

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Mutagenesis-validated functional residues (2):

Position	Phenotype
102	complete loss of e3 ligase activity; when associated with a-104.
104	complete loss of e3 ligase activity; when associated with s-102.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 230 (showing top): GOBP_BEHAVIOR, TGCGCANK_UNKNOWN, GOBP_ADULT_BEHAVIOR, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_ADULT_LOCOMOTORY_BEHAVIOR, MOLENAAR_TARGETS_OF_CCND1_AND_CDK4_UP, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_PROTEIN_POLYUBIQUITINATION, GOBP_RESPONSE_TO_ABIOTIC_STIMULUS, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_BIOTIC_STIMULUS

GO Biological Process (14): adult walking behavior (GO:0007628), response to temperature stimulus (GO:0009266), gene expression (GO:0010467), response to activity (GO:0014823), toll-like receptor 3 signaling pathway (GO:0034138), negative regulation of toll-like receptor 3 signaling pathway (GO:0034140), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), innate immune response (GO:0045087), protein K48-linked ubiquitination (GO:0070936), protein polyubiquitination (GO:0000209), proteasomal protein catabolic process (GO:0010498), protein ubiquitination (GO:0016567), protein catabolic process (GO:0030163), walking behavior (GO:0090659)

GO Molecular Function (5): zinc ion binding (GO:0008270), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (3): endoplasmic reticulum membrane (GO:0005789), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
adult locomotory behavior	1
walking behavior	1
response to abiotic stimulus	1
macromolecule biosynthetic process	1
response to stimulus	1
endolysosomal toll-like receptor signaling pathway	1
toll-like receptor 3 signaling pathway	1
regulation of toll-like receptor 3 signaling pathway	1
negative regulation of cytoplasmic pattern recognition receptor signaling pathway	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
immune response	1
defense response to symbiont	1
protein polyubiquitination	1
protein ubiquitination	1
protein catabolic process	1
protein modification by small protein conjugation	1
macromolecule catabolic process	1
protein metabolic process	1
locomotory behavior	1
transition metal ion binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
binding	1
catalytic activity	1
cation binding	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1028 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RNF170	ERLIN1	O75477	818
RNF170	ERLIN2	O94905	752
RNF170	ITPR1	Q14643	627
RNF170	RNF139	Q8WU17	624
RNF170	RNF103	O00237	603
RNF170	ITPR3	Q14573	594
RNF170	UBE2J1	Q9Y385	588
RNF170	TMEM129	A0AVI4	587
RNF170	MARCHF6	O60337	582
RNF170	RNF5	Q99942	582
RNF170	ZNRF4	Q8WWF5	566
RNF170	TMUB1	Q9BVT8	557
RNF170	AMFR	P26442	525
RNF170	CGRRF1	Q99675	512
RNF170	FAM8A1	Q9UBU6	506

IntAct

33 interactions, top by confidence:

A	B	Type	Score
ERLIN1	ERLIN2	psi-mi:“MI:0914”(association)	0.740
TMUB1	ERLIN2	psi-mi:“MI:0914”(association)	0.660
rep	EIF4E2	psi-mi:“MI:0914”(association)	0.640
RETREG3	PLSCR1	psi-mi:“MI:0914”(association)	0.640
RNF170	PSMA6	psi-mi:“MI:0915”(physical association)	0.560
PSMA6	RNF170	psi-mi:“MI:0915”(physical association)	0.560
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
RNF170	ERLIN1	psi-mi:“MI:0914”(association)	0.530
DUSP3	ERLIN1	psi-mi:“MI:0914”(association)	0.530
GABBR2	RNF170	psi-mi:“MI:0915”(physical association)	0.400
GPC1	SNAP23	psi-mi:“MI:0915”(physical association)	0.400
GPC1	GANAB	psi-mi:“MI:0915”(physical association)	0.400
UBE2U	RNF170	psi-mi:“MI:0915”(physical association)	0.370
	ESYT2	psi-mi:“MI:0914”(association)	0.350
E5	ESYT2	psi-mi:“MI:0914”(association)	0.350
P2RY12	GPR89A	psi-mi:“MI:0914”(association)	0.350
RETREG3		psi-mi:“MI:0914”(association)	0.350
GPR17	TMEM120B	psi-mi:“MI:0914”(association)	0.350
CCR6	GPR89A	psi-mi:“MI:0914”(association)	0.350
GCGR	GPR89A	psi-mi:“MI:0914”(association)	0.350
SLC12A9	PGRMC1	psi-mi:“MI:0914”(association)	0.350
SLC26A8	PSMD12	psi-mi:“MI:0914”(association)	0.350
SLC35B2	NDUFS8	psi-mi:“MI:0914”(association)	0.350

BioGRID (104): RNF170 (Two-hybrid), RNF170 (Biochemical Activity), RNF170 (Affinity Capture-MS), RNF170 (Affinity Capture-MS), RNF170 (Affinity Capture-MS), RNF170 (Affinity Capture-MS), RNF170 (Affinity Capture-MS), RNF170 (Affinity Capture-MS), RNF170 (Affinity Capture-MS), RNF170 (Affinity Capture-MS), RNF170 (Affinity Capture-MS), RNF170 (Affinity Capture-MS), RNF170 (Affinity Capture-MS), RNF170 (Affinity Capture-MS), RNF170 (Affinity Capture-MS)

ESM2 similar proteins: A0M8T1, A3KN28, A4D7R9, A9JRA0, D3ZEH5, F1MK05, O60337, Q07DV5, Q07DW9, Q07E45, Q09YH4, Q09YI5, Q09YJ7, Q09YK8, Q0VCK9, Q108U3, Q28DS3, Q2HJD0, Q2IBE0, Q2IBE8, Q2QL86, Q2QLA6, Q2QLB7, Q2QLD7, Q2QLE8, Q2TBU2, Q3SZ48, Q3TDN2, Q4R910, Q4V888, Q5PPX5, Q5R9W1, Q68FW3, Q6GM44, Q6NYF1, Q6P4H8, Q6ZQ89, Q7SZN2, Q86TM6, Q8CBG9

Diamond homologs: A0JPQ4, A6QQX5, D3YY23, D3Z8N2, F6ZQ54, F8S122, O00478, O00481, O60858, O75677, P18892, P82885, P83234, Q13410, Q14258, Q17RB8, Q1XH17, Q1XH18, Q27J48, Q2XXL4, Q32L60, Q503I2, Q5EBN2, Q5M7V1, Q5R846, Q5R996, Q5TA31, Q5ZMD4, Q61510, Q62556, Q640S6, Q6PGR9, Q6QA27, Q6UX41, Q6UXG8, Q6ZMU5, Q7SZN2, Q7T308, Q7TST0, Q810I1

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	RNF170	ubiquitination
RNF170	“down-regulates activity”	ITPR1	polyubiquitination
RNF170	“down-regulates activity”	ITPR2	polyubiquitination
Erlin	“up-regulates activity”	RNF170	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 33 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
G alpha (i) signalling events	5	8.5×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	2
Uncertain significance	36
Likely benign	5
Benign	4

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
1321939	NM_030954.4(RNF170):c.342C>G (p.Tyr114Ter)	Pathogenic
1331699	NM_030954.4(RNF170):c.518_519del (p.Arg173fs)	Pathogenic
31590	NM_030954.4(RNF170):c.595C>T (p.Arg199Cys)	Pathogenic
4082202	NM_030954.4(RNF170):c.190C>T (p.Arg64Ter)	Pathogenic
1184893	NM_030954.4(RNF170):c.396+3A>G	Likely pathogenic
1691706	NM_030954.4(RNF170):c.321T>G (p.Cys107Trp)	Likely pathogenic

SpliceAI

1905 predictions. Top by Δscore:

Variant	Effect	Δscore
8:42861736:ATTAC:A	donor_loss	1.0000
8:42861737:TTAC:T	donor_loss	1.0000
8:42861738:TAC:T	donor_loss	1.0000
8:42861739:AC:A	donor_loss	1.0000
8:42861740:CT:C	donor_loss	1.0000
8:42861741:TTAC:T	donor_loss	1.0000
8:42861742:TACAG:T	donor_loss	1.0000
8:42861743:A:AC	donor_gain	1.0000
8:42861743:ACAG:A	donor_loss	1.0000
8:42861744:C:CG	donor_gain	1.0000
8:42861744:CAG:C	donor_gain	1.0000
8:42861744:CAGA:C	donor_gain	1.0000
8:42861744:CAGAT:C	donor_gain	1.0000
8:42861857:T:C	acceptor_loss	1.0000
8:42862408:AAC:A	donor_gain	1.0000
8:42862417:T:TA	donor_gain	1.0000
8:42864615:A:AC	donor_gain	1.0000
8:42864615:ACTG:A	donor_gain	1.0000
8:42864616:C:CC	donor_gain	1.0000
8:42864616:CTGC:C	donor_gain	1.0000
8:42869998:GCTT:G	donor_loss	1.0000
8:42869999:CTTAC:C	donor_loss	1.0000
8:42870000:TTA:T	donor_loss	1.0000
8:42870001:TAC:T	donor_loss	1.0000
8:42870002:A:AC	donor_gain	1.0000
8:42870002:A:T	donor_loss	1.0000
8:42870003:C:CA	donor_loss	1.0000
8:42870003:C:CC	donor_gain	1.0000
8:42870003:CCA:C	donor_gain	1.0000
8:42870110:ATCC:A	acceptor_loss	1.0000

AlphaMissense

1692 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:42856238:T:G	D233A	1.000
8:42856241:T:A	D232V	1.000
8:42856241:T:G	D232A	1.000
8:42856242:C:G	D232H	1.000
8:42865434:A:C	C126W	1.000
8:42865435:C:T	C126Y	1.000
8:42865436:A:G	C126R	1.000
8:42870067:A:G	C87R	1.000
8:42856190:C:G	R249P	0.999
8:42856229:A:T	V236D	0.999
8:42856237:A:C	D233E	0.999
8:42856237:A:T	D233E	0.999
8:42856238:T:A	D233V	0.999
8:42856238:T:C	D233G	0.999
8:42856239:C:G	D233H	0.999
8:42856240:A:C	D232E	0.999
8:42856240:A:T	D232E	0.999
8:42856241:T:C	D232G	0.999
8:42856242:C:A	D232Y	0.999
8:42856251:C:A	G229C	0.999
8:42856251:C:G	G229R	0.999
8:42856259:C:T	G226E	0.999
8:42856314:C:G	G208R	0.999
8:42856314:C:T	G208R	0.999
8:42856334:C:A	R201M	0.999
8:42856406:A:G	L177P	0.999
8:42861763:G:C	F163L	0.999
8:42861763:G:T	F163L	0.999
8:42861765:A:G	F163L	0.999
8:42861777:A:C	Y159D	0.999

dbSNP variants (sampled 300 via entrez): RS1000036965 (8:42869411 T>C), RS1000090660 (8:42869911 G>A), RS1000193350 (8:42860204 G>A), RS1000225705 (8:42860569 CA>C), RS1000238304 (8:42861323 A>G), RS1000244988 (8:42892380 G>T), RS1000290626 (8:42867747 G>C), RS1000358407 (8:42897669 G>C), RS1000473445 (8:42895168 A>G), RS1000493090 (8:42858651 C>T), RS1000566764 (8:42858974 G>C), RS1000617718 (8:42896606 G>A,C,T), RS1000637528 (8:42855863 G>A,T), RS1000674149 (8:42851825 G>A,T), RS1000689753 (8:42856450 A>G)

Disease associations

OMIM: gene MIM:614649 | disease phenotypes: MIM:608984, MIM:619686

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal dominant sensory ataxia 1	Strong	Autosomal dominant
spastic paraplegia 85, autosomal recessive	Strong	Autosomal recessive

Mondo (3): autosomal dominant sensory ataxia 1 (MONDO:0012166), spastic paraplegia 85, autosomal recessive (MONDO:0030512), neurodevelopmental disorder (MONDO:0700092)

Orphanet (1): Autosomal recessive spastic paraplegia type 85 (Orphanet:631082)

HPO phenotypes

39 total (30 of 39 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000020	Urinary incontinence
HP:0000473	Torticollis
HP:0000648	Optic atrophy
HP:0001152	Saccadic smooth pursuit interruptions
HP:0001258	Spastic paraplegia
HP:0001260	Dysarthria
HP:0001265	Hyporeflexia
HP:0001270	Motor delay
HP:0001272	Cerebellar atrophy
HP:0001284	Areflexia
HP:0001288	Gait disturbance
HP:0001317	Abnormal cerebellum morphology
HP:0001348	Brisk reflexes
HP:0002015	Dysphagia
HP:0002061	Lower limb spasticity
HP:0002066	Gait ataxia
HP:0002359	Frequent falls
HP:0002403	Positive Romberg sign
HP:0002495	Impaired vibratory sensation
HP:0003409	Distal sensory impairment of all modalities
HP:0003477	Peripheral axonal neuropathy
HP:0003487	Babinski sign
HP:0003596	Middle age onset
HP:0003700	Generalized amyotrophy
HP:0006858	Impaired distal proprioception
HP:0006886	Impaired distal vibration sensation
HP:0006962	Gait instability, worse in the dark
HP:0006986	Upper limb spasticity

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, decreases expression, affects cotreatment	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	increases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
pentabromodiphenyl ether	decreases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
2,3,5-trichloro-6-phenyl-(1,4)benzoquinone	increases expression	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1
Acetaminophen	decreases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation	1
Carbamazepine	affects expression	1
Dexamethasone	affects cotreatment, increases expression	1
Endosulfan	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Malathion	increases expression	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice