CWF19L1

Summary

CWF19L1 (CWF19 like cell cycle control factor 1, HGNC:25613) is a protein-coding gene on chromosome 10q24.31, encoding CWF19-like protein 1 (Q69YN2).

This gene encodes a member of the CWF19 protein family. Mutations in this gene have been associated with autosomal recessive spinocerebellar ataxia-17 and mild cognitive disability. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 55280 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal recessive cerebellar ataxia (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 142 total — 13 pathogenic, 14 likely-pathogenic
• Phenotypes (HPO): 42
• MANE Select transcript: NM_018294

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25613
Approved symbol	CWF19L1
Name	CWF19 like cell cycle control factor 1
Location	10q24.31
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10998, hDrn1
Ensembl gene	ENSG00000095485
Ensembl biotype	protein_coding
OMIM	616120
Entrez	55280

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 8 protein_coding, 2 retained_intron, 2 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000354105, ENST00000466408, ENST00000466955, ENST00000468709, ENST00000473842, ENST00000478047, ENST00000482452, ENST00000496796, ENST00000905383, ENST00000905384, ENST00000921478, ENST00000950160, ENST00000950161, ENST00000950162

RefSeq mRNA: 5 — MANE Select: NM_018294 NM_001303404, NM_001303405, NM_001303406, NM_001303407, NM_018294

CCDS: CCDS7489

Canonical transcript exons

ENST00000354105 — 14 exons

Exon	Start	End
ENSE00001452536	100232298	100233371
ENSE00003514639	100260966	100261044
ENSE00003527235	100246795	100246935
ENSE00003527766	100261979	100262063
ENSE00003538143	100236850	100236969
ENSE00003538616	100245799	100245913
ENSE00003541487	100256262	100256476
ENSE00003545611	100250248	100250332
ENSE00003545685	100253421	100253539
ENSE00003574244	100243698	100243777
ENSE00003594872	100260218	100260319
ENSE00003632204	100267571	100267638
ENSE00003640202	100235667	100235764
ENSE00003687711	100238022	100238231

Expression profiles

Bgee: expression breadth ubiquitous, 216 present calls, max score 90.91.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.7588 / max 265.9175, expressed in 1785 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
111031	11.1669	1774
111032	2.5919	1351

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	90.91	gold quality
mononuclear cell	CL:0000842	90.88	gold quality
leukocyte	CL:0000738	90.82	gold quality
bone marrow	UBERON:0002371	89.16	gold quality
granulocyte	CL:0000094	88.41	gold quality
blood	UBERON:0000178	88.10	gold quality
diaphragm	UBERON:0001103	86.71	gold quality
skin of leg	UBERON:0001511	86.55	gold quality
right testis	UBERON:0004534	86.33	gold quality
tendon of biceps brachii	UBERON:0008188	86.29	silver quality
spleen	UBERON:0002106	86.02	gold quality
tendon	UBERON:0000043	85.88	gold quality
left testis	UBERON:0004533	85.85	gold quality
islet of Langerhans	UBERON:0000006	85.75	gold quality
calcaneal tendon	UBERON:0003701	85.64	gold quality
skin of abdomen	UBERON:0001416	85.62	gold quality
lymph node	UBERON:0000029	85.53	gold quality
bone marrow cell	CL:0002092	85.49	gold quality
mucosa of stomach	UBERON:0001199	85.31	gold quality
ganglionic eminence	UBERON:0004023	85.07	gold quality
cerebellar hemisphere	UBERON:0002245	85.01	gold quality
left ovary	UBERON:0002119	84.99	gold quality
cerebellar cortex	UBERON:0002129	84.98	gold quality
tibial nerve	UBERON:0001323	84.61	gold quality
right uterine tube	UBERON:0001302	84.55	gold quality
testis	UBERON:0000473	84.51	gold quality
zone of skin	UBERON:0000014	84.50	gold quality
tibial artery	UBERON:0007610	84.37	gold quality
popliteal artery	UBERON:0002250	84.36	gold quality
body of uterus	UBERON:0009853	84.36	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.92
E-MTAB-6379	no	374.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

41 targeting CWF19L1, 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-3613-3P	100.00	76.36	7965
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-3975	99.62	65.97	697
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-409-3P	99.50	66.33	1192
HSA-MIR-504-3P	99.30	67.18	1745
HSA-MIR-485-5P	99.10	64.78	1889
HSA-MIR-6884-5P	99.10	64.50	1987
HSA-MIR-7153-3P	99.00	65.35	608
HSA-MIR-12135	98.99	70.26	1814
HSA-MIR-4801	98.96	69.42	2096
HSA-MIR-5006-5P	98.79	66.92	1246
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-583	98.71	67.44	1791
HSA-MIR-7977	98.65	66.18	2590
HSA-MIR-619-5P	98.57	64.97	1988
HSA-MIR-6818-3P	98.56	68.23	1307
HSA-MIR-4731-3P	98.56	68.60	1860
HSA-MIR-4718	98.55	68.61	814
HSA-MIR-4252	98.45	66.37	987

Literature-anchored findings (GeneRIF, showing 9)

• Our findings suggest ERLIN1-CHUK-CWF19L1 variants are associated with early stage of fatty liver accumulation to hepatic inflammation. (PMID:23477746)
• CWF19L1 mutations may be a novel cause of recessive ataxia with developmental delay (PMID:25361784)
• Results of protein-protein interaction between human Dbr1 and factors found in the Intron Large complex identify Xab2 and a novel protein CWF19L1 as specific interactors of DBR1. (PMID:25671812)
• Two pathogenic variants in CWF19L1 were identified in a patient with autosomal recessive cerebellar ataxia. c.37G>C variant was inherited from the father and the c.946A>T variant from the mother. (PMID:26197978)
• Our report corroborates that loss-of-function mutations in CWF19Ll lead to early onset cerebellar ataxia and (progressive) cerebellar atrophy. (PMID:27016154)
• A Novel Variant in CWF19L1 Gene in a Family with Late-Onset Autosomal Recessive Cerebellar Ataxia 17. (PMID:33012273)
• Heterozygous pathogenic variants in CWF19L1 in a Chinese family with spinocerebellar ataxia, autosomal recessive 17. (PMID:36357319)
• Expansion of the phenotypic and molecular spectrum of CWF19L1-related disorder. (PMID:36453471)
• Novel CWF19L1 mutations in patients with spinocerebellar ataxia, autosomal recessive 17. (PMID:37752213)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cwf19l1	ENSDARG00000002128
mus_musculus	Cwf19l1	ENSMUSG00000025200
rattus_norvegicus	Cwf19l1	ENSRNOG00000012763
drosophila_melanogaster	CG7741	FBGN0033615
caenorhabditis_elegans		WBGENE00017534

Paralogs (1): CWF19L2 (ENSG00000152404)

Protein

Protein identifiers

CWF19-like protein 1 — Q69YN2 (reviewed: Q69YN2)

All UniProt accessions (5): Q69YN2, A0A0S2Z5E9, A0A0S2Z5Q6, A0A286YEP9, A0A286YF56

UniProt curated annotations — full annotation on UniProt →

Tissue specificity. Expressed in many brain regions, including cerebellum, thalamus and occipital, parietal and temporal lobes (at protein level). Also expressed in the spinal cord (at protein level).

Disease relevance. Spinocerebellar ataxia, autosomal recessive, 17 (SCAR17) [MIM:616127] A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR17 features include non-progressive congenital cerebellar ataxia, mildly delayed walking with an unsteady gait and frequent falls, dysarthria, dysmetria, hypotonia in the extremities, truncal ataxia, increased reflexes in the lower extremities, and intellectual disability. The disease is caused by variants affecting the gene represented in this entry. A disease-causing mutation has been reported that affects an intronic splice donor site and causes exon 9 skipping, this leads to an out-of-frame stop codon after 60 aberrant amino acids. Patients carrying this mutation exhibit much lower mRNA and protein levels compared to unaffected controls, probably due to mRNA nonsense-mediated decay.

Similarity. Belongs to the CWF19 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q69YN2-1	1	yes
Q69YN2-2	2
Q69YN2-3	3

RefSeq proteins (5): NP_001290333, NP_001290334, NP_001290335, NP_001290336, NP_060764* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006767	Cwf19-like_C_dom-2	Domain
IPR006768	Cwf19-like_C_dom-1	Domain
IPR036265	HIT-like_sf	Homologous_superfamily
IPR040194	Cwf19-like	Family

Pfam: PF04676, PF04677

UniProt features (10 total): sequence variant 4, splice variant 3, chain 1, region of interest 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8RO2	ELECTRON MICROSCOPY	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q69YN2-F1	83.71	0.53

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 153 (showing top): STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_RNA_SPLICING, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, FISCHER_DREAM_TARGETS, NOUZOVA_TRETINOIN_AND_H4_ACETYLATION, GOCC_SPLICEOSOMAL_COMPLEX, GOCC_RIBONUCLEOPROTEIN_COMPLEX, NUYTTEN_NIPP1_TARGETS_DN, GOMF_ENZYME_ACTIVATOR_ACTIVITY, GOMF_ENZYME_REGULATOR_ACTIVITY, KRIGE_RESPONSE_TO_TOSEDOSTAT_6HR_DN, TAYLOR_METHYLATED_IN_ACUTE_LYMPHOBLASTIC_LEUKEMIA, GOBP_MRNA_PROCESSING, GOCC_POST_MRNA_RELEASE_SPLICEOSOMAL_COMPLEX

GO Biological Process (1): mRNA splicing, via spliceosome (GO:0000398)

GO Molecular Function (2): RNA lariat debranching enzyme activator activity (GO:0061632), protein binding (GO:0005515)

GO Cellular Component (1): post-mRNA release spliceosomal complex (GO:0071014)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
RNA lariat debranching enzyme activity	1
ribonuclease activator activity	1
binding	1
spliceosomal complex	1
U5 snRNP	1

Protein interactions and networks

STRING

1134 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CWF19L1	ERLIN1	O75477	572
CWF19L1	C1orf74	Q96LT6	561
CWF19L1	SS18L1	O75177	465
CWF19L1	XAB2	Q9HCS7	462
CWF19L1	ACAD9	Q9H845	438
CWF19L1	YJU2	Q9BW85	429
CWF19L1	DBR1	Q9UK59	422
CWF19L1	CWF19L2	Q2TBE0	420
CWF19L1	USP54	Q70EL1	420
CWF19L1	PPP1R3B	Q86XI6	392
CWF19L1	CFAP119	A1A4V9	367
CWF19L1	CWC22	Q9HCG8	363
CWF19L1	FBXW4	P57775	362
CWF19L1	CCT2	P78371	360
CWF19L1	TFIP11	Q9UBB9	360

IntAct

75 interactions, top by confidence:

A	B	Type	Score
PPIE	AQR	psi-mi:“MI:0914”(association)	0.810
PRPF19	AQR	psi-mi:“MI:0914”(association)	0.790
ISY1	AQR	psi-mi:“MI:0914”(association)	0.740
RALY	HNRNPC	psi-mi:“MI:0914”(association)	0.740
SYF2	AQR	psi-mi:“MI:0914”(association)	0.730
KBTBD7	METTL15	psi-mi:“MI:0914”(association)	0.730
SNRPG	GEMIN2	psi-mi:“MI:0914”(association)	0.710
SNW1	AQR	psi-mi:“MI:0914”(association)	0.650
SNRPA1	HTATSF1	psi-mi:“MI:0914”(association)	0.640
SNRPA1	U2SURP	psi-mi:“MI:0914”(association)	0.640
CWF19L2	CWF19L1	psi-mi:“MI:0915”(physical association)	0.560
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
SNRPE	SNRPGP15	psi-mi:“MI:0914”(association)	0.530
ELAVL2	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
RALYL	CDC40	psi-mi:“MI:0914”(association)	0.530
EIPR1	LDHC	psi-mi:“MI:0914”(association)	0.530
YJU2B	RCCD1	psi-mi:“MI:0914”(association)	0.530
ILF2	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
SNRPE	PRMT5	psi-mi:“MI:0914”(association)	0.530
PPIL1	AQR	psi-mi:“MI:0914”(association)	0.530
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
CWF19L1	H2BC15	psi-mi:“MI:0915”(physical association)	0.400
CWF19L1	SMG7	psi-mi:“MI:0915”(physical association)	0.400
CWF19L1	H2BC5	psi-mi:“MI:0915”(physical association)	0.400
DBR1	CWF19L1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (97): CWF19L1 (Affinity Capture-MS), CWF19L1 (Affinity Capture-MS), CWF19L1 (Affinity Capture-MS), CWF19L1 (Affinity Capture-MS), CWF19L1 (Affinity Capture-MS), CWF19L1 (Affinity Capture-MS), CWF19L1 (Affinity Capture-MS), CWF19L1 (Affinity Capture-MS), CWF19L1 (Affinity Capture-MS), CWF19L1 (Affinity Capture-MS), CWF19L1 (Affinity Capture-MS), CWF19L1 (Affinity Capture-MS), CWF19L1 (Affinity Capture-MS), CWF19L1 (Proximity Label-MS), CWF19L1 (Proximity Label-MS)

ESM2 similar proteins: A0A3L7I2I8, A0FKG7, A1Z3X3, A4GWN3, A5PK39, E9Q4Z2, O00763, O55236, O60733, O60942, P10687, P10894, P29144, P49754, P82922, P97570, P97789, P97819, Q15147, Q2KJA6, Q32PW3, Q5IH13, Q5KU39, Q5R8R4, Q5ZKK2, Q640G7, Q641K1, Q64514, Q64560, Q69YN2, Q6NY98, Q6NYU2, Q7ZVK4, Q80YV4, Q8BPM2, Q8CI33, Q8IVH8, Q8IZH2, Q8K114, Q8QFR2

Diamond homologs: A1Z8J0, O16216, Q5R8R4, Q5RGJ5, Q69YN2, Q8AVL0, Q8CI33, Q69NK8, Q84WU9, Q28C44, Q3LSS0

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 94 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
mRNA Splicing	14	22.6×	1e-13
Processing of Capped Intron-Containing Pre-mRNA	15	18.1×	2e-13
mRNA Splicing - Major Pathway	22	17.7×	2e-19
snRNP Assembly	5	15.6×	7e-04
CHD1 and CHD2 subfamily	9	14.4×	7e-07
Dengue Virus-Host Interactions	21	14.1×	9e-17
mRNA Polyadenylation	9	11.6×	4e-06
Metabolism of RNA	18	11.0×	1e-12

GO biological processes:

GO term	Partners	Fold	FDR
U2-type prespliceosome assembly	6	43.5×	1e-06
spliceosomal snRNP assembly	6	40.5×	1e-06
mRNA splicing, via spliceosome	24	25.6×	6e-25
intracellular protein localization	7	8.5×	1e-03
RNA splicing	8	8.2×	7e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	13
Likely pathogenic	14
Uncertain significance	72
Likely benign	15
Benign	7

Top pathogenic / likely-pathogenic (27)

Variant ID	HGVS	Classification
128882	NM_018294.6(CWF19L1):c.964+1G>A	Pathogenic
1322180	NM_018294.6(CWF19L1):c.520A>T (p.Lys174Ter)	Pathogenic
1675429	NM_018294.6(CWF19L1):c.612del (p.Arg204fs)	Pathogenic
1711123	NM_018294.6(CWF19L1):c.1070G>T (p.Gly357Val)	Pathogenic
2497675	NM_018294.6(CWF19L1):c.1375-2A>G	Pathogenic
253210	NM_018294.6(CWF19L1):c.946A>T (p.Lys316Ter)	Pathogenic
379851	NM_018294.6(CWF19L1):c.850-2A>G	Pathogenic
419610	NM_018294.6(CWF19L1):c.622C>T (p.Arg208Ter)	Pathogenic
4687749	NM_018294.6(CWF19L1):c.1372C>T (p.Gln458Ter)	Pathogenic
504028	NM_018294.6(CWF19L1):c.779del (p.Asp260fs)	Pathogenic
800879	NM_018294.6(CWF19L1):c.605dup (p.Tyr202Ter)	Pathogenic
976765	NM_018294.6(CWF19L1):c.1114C>T (p.Gln372Ter)	Pathogenic
996893	NM_018294.6(CWF19L1):c.708+294_1044+1540del	Pathogenic
1675428	NM_018294.6(CWF19L1):c.1381C>T (p.Gln461Ter)	Likely pathogenic
1685293	NM_018294.6(CWF19L1):c.187+1G>T	Likely pathogenic
1711160	NM_018294.6(CWF19L1):c.820dup (p.Ser274fs)	Likely pathogenic
2429271	NM_018294.6(CWF19L1):c.1045-2A>C	Likely pathogenic
2497673	NM_018294.6(CWF19L1):c.452T>G (p.Ile151Ser)	Likely pathogenic
2629563	NM_018294.6(CWF19L1):c.108+1G>A	Likely pathogenic
3775832	NM_018294.6(CWF19L1):c.1299del (p.Asp434fs)	Likely pathogenic
427092	NM_018294.6(CWF19L1):c.685G>T (p.Val229Phe)	Likely pathogenic
488454	NM_018294.6(CWF19L1):c.1150G>T (p.Glu384Ter)	Likely pathogenic
806557	NM_018294.6(CWF19L1):c.942del (p.Pro315fs)	Likely pathogenic
872772	NM_018294.6(CWF19L1):c.37G>C (p.Asp13His)	Likely pathogenic
984934	NM_018294.6(CWF19L1):c.349G>T (p.Glu117Ter)	Likely pathogenic
987461	NM_018294.6(CWF19L1):c.708+1G>A	Likely pathogenic
996587	NM_018294.6(CWF19L1):c.949C>T (p.Gln317Ter)	Likely pathogenic

SpliceAI

2797 predictions. Top by Δscore:

Variant	Effect	Δscore
10:100233368:CTCC:C	acceptor_gain	1.0000
10:100233369:TCC:T	acceptor_gain	1.0000
10:100233370:CC:C	acceptor_gain	1.0000
10:100233370:CCC:C	acceptor_gain	1.0000
10:100233371:CC:C	acceptor_gain	1.0000
10:100233372:C:CC	acceptor_gain	1.0000
10:100236816:A:AC	donor_gain	1.0000
10:100236817:C:CC	donor_gain	1.0000
10:100236822:C:A	donor_gain	1.0000
10:100238232:C:CC	acceptor_gain	1.0000
10:100243781:CA:C	acceptor_gain	1.0000
10:100243782:A:AC	acceptor_gain	1.0000
10:100243782:A:C	acceptor_gain	1.0000
10:100245797:A:AC	donor_gain	1.0000
10:100245798:C:CC	donor_gain	1.0000
10:100245798:CGAG:C	donor_gain	1.0000
10:100245924:C:CT	acceptor_gain	1.0000
10:100246790:CATA:C	donor_loss	1.0000
10:100246791:ATACC:A	donor_loss	1.0000
10:100246793:A:AT	donor_loss	1.0000
10:100246794:CCA:C	donor_gain	1.0000
10:100246816:T:TA	donor_gain	1.0000
10:100246829:T:TA	donor_gain	1.0000
10:100246932:GATA:G	acceptor_gain	1.0000
10:100246934:TA:T	acceptor_gain	1.0000
10:100246934:TACT:T	acceptor_loss	1.0000
10:100246936:C:CC	acceptor_gain	1.0000
10:100246936:C:CG	acceptor_loss	1.0000
10:100246937:T:C	acceptor_gain	1.0000
10:100246937:T:G	acceptor_loss	1.0000

AlphaMissense

3541 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:100243751:A:G	C331R	0.999
10:100243760:A:G	C328R	0.999
10:100235733:A:T	V469D	0.998
10:100238034:G:C	H414Q	0.998
10:100238034:G:T	H414Q	0.998
10:100238036:G:C	H414D	0.998
10:100238185:A:G	L364P	0.998
10:100243749:G:C	C331W	0.998
10:100243750:C:G	C331S	0.998
10:100243750:C:T	C331Y	0.998
10:100243751:A:T	C331S	0.998
10:100243752:A:C	F330L	0.998
10:100243752:A:T	F330L	0.998
10:100243754:A:G	F330L	0.998
10:100243758:G:C	C328W	0.998
10:100243759:C:T	C328Y	0.998
10:100246925:G:T	A240E	0.998
10:100253421:C:G	R208P	0.998
10:100262052:C:T	G12E	0.998
10:100233320:C:A	W508C	0.997
10:100233320:C:G	W508C	0.997
10:100233322:A:G	W508R	0.997
10:100233322:A:T	W508R	0.997
10:100235673:A:G	F489S	0.997
10:100235709:A:G	L477P	0.997
10:100236906:C:G	A440P	0.997
10:100238065:A:T	V404D	0.997
10:100238166:G:C	H370Q	0.997
10:100238166:G:T	H370Q	0.997
10:100243750:C:A	C331F	0.997

dbSNP variants (sampled 300 via entrez): RS1000045952 (10:100263920 A>G), RS1000290903 (10:100257778 C>T), RS1000291416 (10:100234140 T>A), RS1000347814 (10:100264451 G>A), RS1000434765 (10:100263444 CA>C), RS1000534064 (10:100259284 C>T), RS1000624409 (10:100262845 T>C), RS1000718786 (10:100262448 T>C), RS1000807106 (10:100251868 G>A), RS1000821153 (10:100269174 G>A), RS1000834562 (10:100264273 C>T), RS1000866778 (10:100238812 G>A), RS1000872899 (10:100246601 T>C), RS1001096657 (10:100239142 C>G), RS1001152180 (10:100237200 T>C,G)

Disease associations

OMIM: gene MIM:616120 | disease phenotypes: MIM:616127

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal recessive spinocerebellar ataxia 17	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
autosomal recessive cerebellar ataxia	Definitive	AR

Mondo (2): autosomal recessive spinocerebellar ataxia 17 (MONDO:0014503), intellectual disability (MONDO:0001071)

Orphanet (2): Autosomal recessive cerebellar ataxia due to CWF19L1 deficiency (Orphanet:453521), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

42 total (30 of 42 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000486	Strabismus
HP:0000574	Thick eyebrow
HP:0000657	Oculomotor apraxia
HP:0000664	Synophrys
HP:0000666	Horizontal nystagmus
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001256	Mild intellectual disability
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001272	Cerebellar atrophy
HP:0001274	Agenesis of corpus callosum
HP:0001310	Dysmetria
HP:0001320	Cerebellar vermis hypoplasia
HP:0001321	Cerebellar hypoplasia
HP:0001332	Dystonia
HP:0001347	Hyperreflexia
HP:0001350	Slurred speech
HP:0002066	Gait ataxia
HP:0002070	Limb ataxia
HP:0002078	Truncal ataxia
HP:0002080	Intention tremor
HP:0002136	Broad-based gait
HP:0002312	Clumsiness
HP:0002317	Unsteady gait
HP:0002342	Moderate intellectual disability
HP:0002359	Frequent falls

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009731_17	Blood protein levels in cardiovascular risk	3.000000e-13

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008183	interleukin 27 receptor subunit alpha measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol F	affects cotreatment, increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
arsenite	affects binding, increases reaction	1
sodium arsenite	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
chromium hexavalent ion	decreases expression, increases abundance	1
ICG 001	decreases expression	1
Bortezomib	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Arsenic Trioxide	decreases expression	1
Atrazine	decreases expression	1
Cadmium	increases abundance, increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Endosulfan	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Indomethacin	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Lead	affects methylation	1
Plant Extracts	affects cotreatment, increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Antirheumatic Agents	decreases expression	1
Cadmium Chloride	increases abundance, increases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
NCT02714868	Not specified	COMPLETED	Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications)
NCT02721394	Not specified	UNKNOWN	FCT With Young Children With ID in the UK: A Feasibility Project V.1
NCT02746614	Not specified	COMPLETED	Psychomotor Therapy Effects in Adaptive Behavior and Motor Proficiency in Intellectual Disability
NCT02836405	Not specified	COMPLETED	TMS for the Investigation of Brain Plasticity in Autism Spectrum Disorders