Autosomal recessive spinocerebellar ataxia 20

Summary

Autosomal recessive spinocerebellar ataxia 20 (MONDO:0014601) is a disease caused by SNX14 (GenCC Definitive), with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: SNX14 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 52
• Phenotypes (HPO): 54

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		30	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

54 HPO clinical features (Orphanet curated; top 50 by frequency):

HPO ID	Term	Frequency
HP:0000280	Coarse facial features	Very frequent (80-99%)
HP:0000750	Delayed speech and language development	Very frequent (80-99%)
HP:0002194	Delayed gross motor development	Very frequent (80-99%)
HP:0007360	Aplasia/Hypoplasia of the cerebellum	Very frequent (80-99%)
HP:0010862	Delayed fine motor development	Very frequent (80-99%)
HP:0010864	Intellectual disability, severe	Very frequent (80-99%)
HP:0011344	Severe global developmental delay	Very frequent (80-99%)
HP:0000158	Macroglossia	Frequent (30-79%)
HP:0000407	Sensorineural hearing impairment	Frequent (30-79%)
HP:0000639	Nystagmus	Frequent (30-79%)
HP:0000729	Autistic behavior	Frequent (30-79%)
HP:0001251	Ataxia	Frequent (30-79%)
HP:0001252	Hypotonia	Frequent (30-79%)
HP:0001344	Absent speech	Frequent (30-79%)
HP:0002007	Frontal bossing	Frequent (30-79%)
HP:0002136	Broad-based gait	Frequent (30-79%)
HP:0002751	Kyphoscoliosis	Frequent (30-79%)
HP:0004482	Relative macrocephaly	Frequent (30-79%)
HP:0011842	Abnormality of skeletal morphology	Frequent (30-79%)
HP:0100540	Palpebral edema	Frequent (30-79%)
HP:0000218	High palate	Occasional (5-29%)
HP:0000289	Broad philtrum	Occasional (5-29%)
HP:0000293	Full cheeks	Occasional (5-29%)
HP:0000307	Pointed chin	Occasional (5-29%)
HP:0000343	Long philtrum	Occasional (5-29%)
HP:0000350	Small forehead	Occasional (5-29%)
HP:0000431	Wide nasal bridge	Occasional (5-29%)
HP:0000506	Telecanthus	Occasional (5-29%)
HP:0000678	Dental crowding	Occasional (5-29%)
HP:0000768	Pectus carinatum	Occasional (5-29%)
HP:0001156	Brachydactyly	Occasional (5-29%)
HP:0001250	Seizure	Occasional (5-29%)
HP:0001257	Spasticity	Occasional (5-29%)
HP:0001265	Hyporeflexia	Occasional (5-29%)
HP:0001433	Hepatosplenomegaly	Occasional (5-29%)
HP:0001631	Atrial septal defect	Occasional (5-29%)
HP:0001643	Patent ductus arteriosus	Occasional (5-29%)
HP:0001762	Talipes equinovarus	Occasional (5-29%)
HP:0002002	Deep philtrum	Occasional (5-29%)
HP:0002186	Apraxia	Occasional (5-29%)
HP:0002219	Facial hypertrichosis	Occasional (5-29%)
HP:0002500	Abnormal cerebral white matter morphology	Occasional (5-29%)
HP:0002684	Thickened calvaria	Occasional (5-29%)
HP:0003487	Babinski sign	Occasional (5-29%)
HP:0005280	Depressed nasal bridge	Occasional (5-29%)
HP:0006951	Retrocerebellar cyst	Occasional (5-29%)
HP:0008443	Spinal deformities	Occasional (5-29%)
HP:0010471	Oligosacchariduria	Occasional (5-29%)
HP:0012110	Hypoplasia of the pons	Occasional (5-29%)
HP:0012385	Camptodactyly	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal recessive spinocerebellar ataxia 20
Mondo ID	MONDO:0014601
OMIM	616354
Orphanet	397709
DOID	DOID:0080066
UMLS	C5190595
MedGen	1684324
GARD	0017636
Is cancer (heuristic)	no

Also known as: autosomal recessive cerebellar ataxia caused by mutation in SNX14 · autosomal recessive spinocerebellar ataxia type 20 · intellectual disability-coarse face-macrocephaly-cerebellar hypoplasia syndrome · SCAR20 · SNX14 autosomal recessive cerebellar ataxia · spinocerebellar ataxia, autosomal recessive 20 · spinocerebellar ataxia, autosomal recessive type 20

Data availability: 52 ClinVar variants · 6 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › autosomal recessive spinocerebellar ataxia 20

Related subtypes (216): polymicrogyria, congenital myasthenic syndrome with tubular aggregates, prenatal-onset spinal muscular atrophy with congenital bone fractures, anencephaly, cerebral cavernous malformation, meningocele, progressive external ophthalmoplegia, congenital nystagmus, congenital toxoplasmosis, congenital contractural arachnodactyly, congenital trigeminal anesthesia, familial congenital palsy of trochlear nerve, Myhre syndrome, Aase-Smith syndrome, KBG syndrome, autosomal dominant primary microcephaly, Mobius syndrome, MYH7-related skeletal myopathy, congenital stationary night blindness autosomal dominant 2, Prader-Willi syndrome, congenital myopathy 7A, myosin storage, autosomal dominant, Smith-Magenis syndrome, spina bifida, Freeman-Sheldon syndrome, isolated cerebellar hypoplasia/agenesis, Chediak-Higashi syndrome, Cohen syndrome, multiple pterygium-malignant hyperthermia syndrome, corpus callosum, agenesis of, congenital lactic acidosis, Saguenay-Lac-Saint-Jean type, facial dysmorphism-macrocephaly-myopia-Dandy-Walker malformation syndrome, diastematomyelia, EEM syndrome, Mowat-Wilson syndrome, Johanson-Blizzard syndrome, intellectual disability, Buenos-Aires type, myasthenia, congenital, refractory to acetylcholinesterase inhibitors, congenital myasthenic syndrome 6, Bailey-Bloch congenital myopathy, congenital stationary night blindness 1B, radioulnar synostosis-developmental delay-hypotonia syndrome, Schinzel-Giedion syndrome, schizencephaly, intellectual disability, Wolff type, X-linked intellectual disability-plagiocephaly syndrome, X-linked adrenal hypoplasia congenita, syndromic X-linked intellectual disability 7, syndromic X-linked intellectual disability Shashi type, syndromic X-linked intellectual disability Lubs type, syndromic X-linked intellectual disability Abidi type, syndromic X-linked intellectual disability Siderius type, X-linked intellectual disability, Cabezas type, X-linked intellectual disability-cubitus valgus-dysmorphism syndrome, syndromic X-linked intellectual disability Claes-Jensen type, moyamoya angiopathy-short stature-facial dysmorphism-hypergonadotropic hypogonadism syndrome, multiple congenital anomalies-hypotonia-seizures syndrome 2, developmental and epileptic encephalopathy, 36, blepharophimosis - intellectual disability syndrome, MKB type, X-linked intellectual disability-short stature-overweight syndrome, intellectual disability, X-linked, syndromic 33, syndromic X-linked intellectual disability 34, infantile-onset X-linked spinal muscular atrophy, syndromic X-linked intellectual disability 5, holoprosencephaly-hypokinesia-congenital contractures syndrome, X-linked intellectual disability with marfanoid habitus, Wieacker-Wolff syndrome, MERRF syndrome, macrocephaly-spastic paraplegia-dysmorphism syndrome, intellectual disability-sparse hair-brachydactyly syndrome, myofibrillar myopathy 1, isolated hereditary congenital facial paralysis, fibrosis of extraocular muscles, congenital, 2, Pierpont syndrome, congenital cataracts-facial dysmorphism-neuropathy syndrome, Bohring-Opitz syndrome, PHACE syndrome, B4GALT1-congenital disorder of glycosylation, developmental malformations-deafness-dystonia syndrome, sensory ataxic neuropathy, dysarthria, and ophthalmoparesis, AICA-ribosiduria, myofibrillar myopathy 3, fibrosis of extraocular muscles, congenital, 3c, myofibrillar myopathy 4, myofibrillar myopathy 5, cone-rod synaptic disorder, congenital nonprogressive, congenital stationary night blindness autosomal dominant 3, congenital stationary night blindness autosomal dominant 1, intellectual disability, autosomal recessive 12, progressive myoclonic epilepsy type 3, chromosome 15q13.3 microdeletion syndrome, combined pituitary hormone deficiencies, genetic form, congenital stationary night blindness 1D, DYRK1A-related intellectual disability syndrome, Pitt-Hopkins-like syndrome 2, developmental and epileptic encephalopathy, 15, Schuurs-Hoeijmakers syndrome, severe intellectual disability-poor language-strabismus-grimacing face-long fingers syndrome, severe intellectual disability-progressive spastic diplegia syndrome, hypotonia, infantile, with psychomotor retardation and characteristic facies, developmental and epileptic encephalopathy, 18, CTCF-related neurodevelopmental disorder, autism spectrum disorder due to AUTS2 deficiency, developmental and epileptic encephalopathy, 23, ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder, Bardet-Biedl syndrome 11, cerebellar-facial-dental syndrome, fibrosis of extraocular muscles, congenital, 5, congenital myasthenic syndrome 15, lethal fetal cerebrorenogenitourinary agenesis/hypoplasia syndrome, autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome, congenital myasthenic syndrome 18, Houge-Janssens syndrome 1, intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome, congenital stationary night blindness 1G, hypomyelinating leukodystrophy 10, developmental and epileptic encephalopathy, 50, congenital insensitivity to pain-hypohidrosis syndrome, macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome, SLC39A8-CDG, spastic paraplegia-severe developmental delay-epilepsy syndrome, cardiac anomalies - developmental delay - facial dysmorphism syndrome, severe intellectual disability-corpus callosum agenesis-facial dysmorphism-cerebellar ataxia syndrome, intellectual disability, autosomal recessive 53, TELO2-related intellectual disability-neurodevelopmental disorder, micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome, autosomal recessive limb-girdle muscular dystrophy type 2Y, myofibrillar myopathy 7, short stature-brachydactyly-obesity-global developmental delay syndrome, autosomal recessive limb-girdle muscular dystrophy type 2R1, severe microbrachycephaly-intellectual disability-athetoid cerebral palsy syndrome, congenital laryngeal palsy, congenital or early infantile CACH syndrome, congenital epulis, severe congenital nemaline myopathy, intermediate nemaline myopathy, typical nemaline myopathy, childhood-onset nemaline myopathy, adult-onset nemaline myopathy, qualitative or quantitative defects of protein involved in O-glycosylation of alpha-dystroglycan, holoprosencephaly, congenital insensitivity to pain with hyperhidrosis, congenital hydrocephalus, familial congenital mirror movements, macrocephaly-short stature-paraplegia syndrome, cephalocele, mitochondrial neurogastrointestinal encephalomyopathy, X-linked intellectual disability-hypogonadism-ichthyosis-obesity-short stature syndrome, 7p22.1 microduplication syndrome, congenital achiasma, congenital retinal arteriovenous communication, 3q27.3 microdeletion syndrome, Prader-Willi-like syndrome, 9q31.1q31.3 microdeletion syndrome, congenital oculomotor nerve palsy, congenital abducens nerve palsy, neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-hip dysplasia syndrome, congenital insensitivity to pain with severe intellectual disability, X-linked intellectual disability-cerebellar hypoplasia-spondylo-epiphyseal dysplasia syndrome, global developmental delay-visual anomalies-progressive cerebellar atrophy-truncal hypotonia syndrome, lissencephaly spectrum disorders, hyaline body myopathy, 22q11.2 deletion syndrome, craniorachischisis, Leber congenital amaurosis, Ritscher-Schinzel syndrome, Rubinstein-Taybi syndrome, X-linked intellectual disability-hypogammaglobulinemia-progressive neurological deterioration syndrome, X-linked intellectual disability-epilepsy-progressive joint contractures-dysmorphism syndrome, X-linked intellectual disability, Pai type, X-linked intellectual disability, Stevenson type, X-linked intellectual disability, Stoll type, congenital muscular dystrophy, congenital vitreoretinal dysplasia, periventricular nodular heterotopia, postsynaptic congenital myasthenic syndrome, subcortical band heterotopia, congenital fibrosis of extraocular muscles type 1, Al Gazali Khidr Prem Chandran syndrome, distal arthrogryposis Moore weaver type, congenital myotonic dystrophy, myasthenic syndrome, congenital, 7B, presynaptic, autosomal recessive, intellectual disability, autosomal dominant 47, intellectual disability, autosomal dominant 48, spondyloepiphyseal dysplasia, sensorineural hearing loss, impaired intellectual development, and leber congenital amaurosis, myasthenic syndrome, congenital, 23, presynaptic, myasthenic syndrome, congenital, 24, presynaptic, myasthenic syndrome, congenital, 25, presynaptic, developmental and epileptic encephalopathy, 77, night blindness, congenital stationary, type1i, neuropathy, congenital hypomelinating, congenital axonal neuropathy with encephalopathy, developmental and epileptic encephalopathy, 73, PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome, isolated exencephaly, myasthenic syndrome, congenital, 22, intellectual developmental disorder with gastrointestinal difficulties and high pain threshold, intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies, 9q33.3q34.11 microdeletion syndrome, congenital labioscrotal agenesis-cerebellar malformation-corneal dystrophy-facial dysmorphism syndrome, early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome, SIN3A-related intellectual disability syndrome, childhood-onset motor and cognitive regression syndrome with extrapyramidal movement disorder, X-linked congenital stationary night blindness, neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies, FOXG1 disorder, alpha-actinopathy, TPM3-related myopathy, X-linked recessive mitochondrial myopathy, RYR1-related myopathy, TTN-related myopathy, TPM2-related myopathy, myopathy caused by variation in POMGNT1, central hypoventilation syndrome, congenital, 1, with or without Hirschsprung disease, segmental spinal dysgenesis, myopathy, myofibrillar, 13, with rimmed vacuoles, congenital neuronal ceroid lipofuscinosis 10

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

52 retrieved; paginated sample, class counts are floors:

16 pathogenic, 15 uncertain significance, 15 likely pathogenic, 3 conflicting classifications of pathogenicity, 2 pathogenic/likely pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1325109	NM_153816.6(SNX14):c.252C>G (p.Tyr84Ter)	SNX14	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
190314	NM_153816.6(SNX14):c.2596C>T (p.Gln866Ter)	SNX14	Pathogenic	no assertion criteria provided
190315	NM_153816.2(SNX14):c.1108+1181_2108-2342del	SNX14	Pathogenic	no assertion criteria provided
190316	NM_153816.6(SNX14):c.645dup (p.Glu216fs)	SNX14	Pathogenic	no assertion criteria provided
190317	NM_153816.6(SNX14):c.1894+1G>T	SNX14	Pathogenic/Likely pathogenic	no assertion criteria provided
190318	NM_153816.6(SNX14):c.1132C>T (p.Arg378Ter)	SNX14	Pathogenic	criteria provided, multiple submitters, no conflicts
190319	NM_153816.6(SNX14):c.428T>A (p.Leu143Ter)	SNX14	Pathogenic	no assertion criteria provided
190320	NM_153816.6(SNX14):c.2670del (p.Lys889_Cys890insTer)	SNX14	Pathogenic	criteria provided, multiple submitters, no conflicts
2572991	NM_153816.6(SNX14):c.1878del (p.Lys626fs)	SNX14	Pathogenic	criteria provided, single submitter
2573004	NM_153816.6(SNX14):c.2148+1G>T	SNX14	Pathogenic	criteria provided, single submitter
268133	NM_153816.6(SNX14):c.1108G>A (p.Glu370Lys)	SNX14	Pathogenic	no assertion criteria provided
373031	NM_153816.6(SNX14):c.1108G>T (p.Glu370Ter)	SNX14	Pathogenic	criteria provided, multiple submitters, no conflicts
375550	NM_153816.6(SNX14):c.1707_1708insTTTTTTTTTTT (p.Pro570fs)	SNX14	Pathogenic	criteria provided, single submitter
3897619	NM_153816.6(SNX14):c.1811-8A>G	SNX14	Pathogenic	criteria provided, single submitter
4083499	GRCh37/hg19 6q14.3(chr6:86235844-86253478)x0	SNX14	Pathogenic	criteria provided, single submitter
4292559	NM_153816.6(SNX14):c.1475+1G>A	SNX14	Pathogenic	criteria provided, single submitter
522726	NM_153816.6(SNX14):c.331C>T (p.Arg111Ter)	SNX14	Pathogenic	criteria provided, multiple submitters, no conflicts
802248	NM_153816.6(SNX14):c.1608+1G>T	SNX14	Pathogenic	criteria provided, single submitter
2433658	NM_153816.6(SNX14):c.44_45del (p.Arg15fs)	SNX14	Likely pathogenic	criteria provided, single submitter
2497676	NM_153816.6(SNX14):c.462-589A>G	SNX14	Likely pathogenic	criteria provided, single submitter
2573000	NM_153816.6(SNX14):c.2746-2A>G	SNX14	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2627362	NC_000006.11:g.(86251762_86252899)_(86259598_86267693)dup	SNX14	Likely pathogenic	criteria provided, single submitter
3336800	NM_153816.6(SNX14):c.2506G>T (p.Glu836Ter)	SNX14	Likely pathogenic	criteria provided, single submitter
3385143	NM_153816.6(SNX14):c.262-1G>A	SNX14	Likely pathogenic	criteria provided, single submitter
3731483	NM_153816.6(SNX14):c.28C>T (p.Gln10Ter)	SNX14	Likely pathogenic	criteria provided, single submitter
3897012	NM_153816.6(SNX14):c.1678C>T (p.Arg560Ter)	SNX14	Likely pathogenic	criteria provided, single submitter
3897618	NM_153816.6(SNX14):c.1883del (p.Thr628fs)	SNX14	Likely pathogenic	criteria provided, single submitter
422470	NM_153816.6(SNX14):c.2557+1G>A	SNX14	Likely pathogenic	criteria provided, single submitter
4293279	NM_153816.6(SNX14):c.455G>A (p.Trp152Ter)	SNX14	Likely pathogenic	criteria provided, single submitter
4293814	NM_153816.6(SNX14):c.2653+1G>A	SNX14	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
SNX14	Definitive	Autosomal recessive	autosomal recessive spinocerebellar ataxia 20	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SNX14	Orphanet:397709	Intellectual disability-coarse face-macrocephaly-cerebellar hypotrophy syndrome
MT-CYB	Orphanet:104	Leber hereditary optic neuropathy
MT-CYB	Orphanet:137675	Histiocytoid cardiomyopathy
MT-CYB	Orphanet:1460	Isolated complex III deficiency

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SNX14	HGNC:14977	ENSG00000135317	Q9Y5W7	Sorting nexin-14	gencc,clinvar
MT-CYB	HGNC:7427	ENSG00000198727	P00156	Cytochrome b	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SNX14	Sorting nexin-14	Plays a role in maintaining normal neuronal excitability and synaptic transmission.
MT-CYB	Cytochrome b	Component of the ubiquinol-cytochrome c reductase complex (complex III or cytochrome b-c1 complex) that is part of the mitochondrial respiratory chain.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.0

Family distribution

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

Family	Genes	Fold	FDR
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SNX14	Other/Unknown	no		PX_dom, Phox_assoc, Sorting_nexin_C
MT-CYB	Other/Unknown	no		Cyt_b/b6_N, Cyt_b/b6_C, Di-haem_cyt_TM

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	1
left testis	1
right testis	1
apex of heart	1
pituitary gland	1
zone of skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SNX14	255	ubiquitous	marker	left testis, right testis, calcaneal tendon
MT-CYB	134	ubiquitous	marker	apex of heart, pituitary gland, zone of skin

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MT-CYB	3,317
SNX14	1,324

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MT-CYB	P00156	5
SNX14	Q9Y5W7	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 2 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Complex III assembly	1	439.2×	0.007	MT-CYB
Mitochondrial translation termination	1	109.8×	0.011	MT-CYB
Respiratory electron transport	1	95.2×	0.011	MT-CYB

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
response to D-galactosamine	1	8426.0×	0.002	MT-CYB
response to cobalamin	1	4213.0×	0.002	MT-CYB
electron transport coupled proton transport	1	2106.5×	0.003	MT-CYB
response to mercury ion	1	1203.7×	0.004	MT-CYB
response to glucagon	1	842.6×	0.004	MT-CYB
response to copper ion	1	766.0×	0.004	MT-CYB
mitochondrial electron transport, ubiquinol to cytochrome c	1	648.1×	0.004	MT-CYB
response to hyperoxia	1	561.7×	0.004	MT-CYB
response to cadmium ion	1	366.4×	0.006	MT-CYB
postsynaptic modulation of chemical synaptic transmission	1	337.0×	0.006	SNX14
animal organ regeneration	1	300.9×	0.006	MT-CYB
cellular respiration	1	216.1×	0.007	MT-CYB
autophagosome maturation	1	175.5×	0.008	SNX14
response to calcium ion	1	159.0×	0.009	MT-CYB
response to toxic substance	1	105.3×	0.012	MT-CYB
response to ethanol	1	73.3×	0.016	MT-CYB
response to hypoxia	1	47.9×	0.023	MT-CYB
response to xenobiotic stimulus	1	34.5×	0.030	MT-CYB
protein transport	1	21.9×	0.045	SNX14

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SNX14	0	0
MT-CYB	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

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

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	SNX14, MT-CYB

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SNX14	0	—
MT-CYB	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.