SLC39A8-CDG

Summary

SLC39A8-CDG (MONDO:0014746) is a disease caused by SLC39A8 (GenCC Definitive), with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: SLC39A8 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 29
• Phenotypes (HPO): 41

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		10	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

41 HPO clinical features (Orphanet curated; top 41 by frequency):

HPO ID	Term	Frequency
HP:0002187	Intellectual disability, profound	Very frequent (80-99%)
HP:0006829	Severe muscular hypotonia	Very frequent (80-99%)
HP:0008277	Abnormality of zinc homeostasis	Very frequent (80-99%)
HP:0012301	Type II transferrin isoform profile	Very frequent (80-99%)
HP:0012736	Profound global developmental delay	Very frequent (80-99%)
HP:0032098	Hypomanganesemia	Very frequent (80-99%)
HP:0000486	Strabismus	Frequent (30-79%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0001272	Cerebellar atrophy	Frequent (30-79%)
HP:0001531	Failure to thrive in infancy	Frequent (30-79%)
HP:0002120	Cerebral cortical atrophy	Frequent (30-79%)
HP:0002421	Poor head control	Frequent (30-79%)
HP:0002540	Inability to walk	Frequent (30-79%)
HP:0004322	Short stature	Frequent (30-79%)
HP:0025405	Visual fixation instability	Frequent (30-79%)
HP:0000365	Hearing impairment	Occasional (5-29%)
HP:0000369	Low-set ears	Occasional (5-29%)
HP:0000483	Astigmatism	Occasional (5-29%)
HP:0000540	Hypermetropia	Occasional (5-29%)
HP:0000639	Nystagmus	Occasional (5-29%)
HP:0000938	Osteopenia	Occasional (5-29%)
HP:0001332	Dystonia	Occasional (5-29%)
HP:0001347	Hyperreflexia	Occasional (5-29%)
HP:0001363	Craniosynostosis	Occasional (5-29%)
HP:0001392	Abnormality of the liver	Occasional (5-29%)
HP:0002119	Ventriculomegaly	Occasional (5-29%)
HP:0002465	Poor speech	Occasional (5-29%)
HP:0002490	Increased CSF lactate	Occasional (5-29%)
HP:0002521	Hypsarrhythmia	Occasional (5-29%)
HP:0002719	Recurrent infections	Occasional (5-29%)
HP:0002882	Sudden episodic apnea	Occasional (5-29%)
HP:0002928	Decreased activity of the pyruvate dehydrogenase complex	Occasional (5-29%)
HP:0002987	Elbow flexion contracture	Occasional (5-29%)
HP:0006380	Knee flexion contracture	Occasional (5-29%)
HP:0006558	Decreased mitochondrial complex III activity in liver tissue	Occasional (5-29%)
HP:0008314	Decreased activity of mitochondrial complex II	Occasional (5-29%)
HP:0008347	Decreased activity of mitochondrial complex IV	Occasional (5-29%)
HP:0008873	Disproportionate short-limb short stature	Occasional (5-29%)
HP:0009826	Limb undergrowth	Occasional (5-29%)
HP:0010621	Cutaneous syndactyly of toes	Occasional (5-29%)
HP:0012368	Flat face	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	SLC39A8-CDG
Mondo ID	MONDO:0014746
OMIM	616721
Orphanet	468699
DOID	DOID:0070266
UMLS	C4225234
MedGen	899837
GARD	0017846
Is cancer (heuristic)	no

Also known as: carbohydrate deficient glycoprotein syndrome type IIn · CDG syndrome type IIn · CDG-IIn · CDG2N · congenital disorder of glycosylation type 2n · congenital disorder of glycosylation type IIn · congenital disorder of glycosylation, type IIn · SLC39A8 deficiency

Data availability: 29 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › SLC39A8-CDG

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, autosomal recessive spinocerebellar ataxia 20, 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, 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

29 retrieved; paginated sample, class counts are floors:

14 uncertain significance, 5 likely pathogenic, 5 pathogenic, 3 conflicting classifications of pathogenicity, 1 benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
218898	NM_022154.5(SLC39A8):c.[97G>A;1004G>C]		Pathogenic	no assertion criteria provided
424755	NM_022154.5(SLC39A8):c.[1019T>A];[112G>C]		Pathogenic	criteria provided, single submitter
424757	NM_022154.5(SLC39A8):c.[97G>A;1004G>C];[c.610G>T]		Pathogenic	criteria provided, single submitter
218895	NM_001135146.2(SLC39A8):c.112G>C (p.Gly38Arg)	LOC129992876	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1210340	NM_001135146.2(SLC39A8):c.218dup (p.Cys74fs)	SLC39A8	Pathogenic	criteria provided, single submitter
1686211	NM_001135146.2(SLC39A8):c.1283C>T (p.Thr428Ile)	SLC39A8	Pathogenic	criteria provided, single submitter
3897887	NM_022154.5:c.[937C>T];[610G>T]		Likely pathogenic	criteria provided, single submitter
1030797	NM_001135146.2(SLC39A8):c.1026T>A (p.Cys342Ter)	LOC126807125	Likely pathogenic	criteria provided, single submitter
1030798	NM_001135146.2(SLC39A8):c.316C>T (p.Gln106Ter)	SLC39A8	Likely pathogenic	criteria provided, single submitter
218896	NM_001135146.2(SLC39A8):c.1019T>A (p.Ile340Asn)	SLC39A8	Likely pathogenic	criteria provided, single submitter
869411	NM_001135146.2(SLC39A8):c.338G>C (p.Cys113Ser)	SLC39A8	Likely pathogenic	criteria provided, single submitter
1013495	NM_001135146.2(SLC39A8):c.965T>C (p.Ile322Thr)	LOC126807125	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
242446	NM_001135146.2(SLC39A8):c.97G>A (p.Val33Met)	LOC129992876	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
218897	NM_001135146.2(SLC39A8):c.610G>T (p.Gly204Cys)	SLC39A8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1030796	NM_001135146.2(SLC39A8):c.1020C>G (p.Ile340Met)	LOC126807125	Uncertain significance	criteria provided, single submitter
1030799	NM_001135146.2(SLC39A8):c.923C>T (p.Thr308Met)	LOC126807125	Uncertain significance	criteria provided, single submitter
3237493	NM_001135146.2(SLC39A8):c.1120T>A (p.Cys374Ser)	LOC126807125	Uncertain significance	criteria provided, single submitter
424603	NM_001135146.2(SLC39A8):c.1166A>G (p.Asn389Ser)	LOC126807125	Uncertain significance	criteria provided, multiple submitters, no conflicts
4529493	NM_001135146.2(SLC39A8):c.1076G>A (p.Gly359Glu)	LOC126807125	Uncertain significance	criteria provided, single submitter
800792	NM_001135146.2(SLC39A8):c.915G>C (p.Trp305Cys)	LOC126807125	Uncertain significance	no assertion criteria provided
1805152	NM_001135146.2(SLC39A8):c.16_28del (p.Ala6fs)	LOC129992876	Uncertain significance	criteria provided, single submitter
4796704	NM_001135146.2(SLC39A8):c.109T>C (p.Phe37Leu)	LOC129992876	Uncertain significance	criteria provided, single submitter
4277763	NM_020706.2(SCAF4):c.409G>C (p.Gly137Arg)	SCAF4	Uncertain significance	criteria provided, single submitter
1679260	NM_001135146.2(SLC39A8):c.500G>C (p.Gly167Ala)	SLC39A8	Uncertain significance	criteria provided, single submitter
2436029	NM_001135146.2(SLC39A8):c.1372G>C (p.Glu458Gln)	SLC39A8	Uncertain significance	criteria provided, single submitter
2436030	NM_001135146.2(SLC39A8):c.*1062C>T	SLC39A8	Uncertain significance	criteria provided, single submitter
432927	NM_001135146.2(SLC39A8):c.1097dup (p.Leu366fs)	SLC39A8	Uncertain significance	criteria provided, multiple submitters, no conflicts
635074	NM_001135146.2(SLC39A8):c.337T>C (p.Cys113Arg)	SLC39A8	Uncertain significance	criteria provided, multiple submitters, no conflicts
1269652	NM_001135146.2(SLC39A8):c.552+48C>T	SLC39A8	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 2 · 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
SLC39A8	Definitive	Autosomal recessive	SLC39A8-CDG	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC39A8	Orphanet:468699	SLC39A8-CDG
SCAF4	Orphanet:528084	Non-specific syndromic intellectual disability

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
SLC39A8	HGNC:20862	ENSG00000138821	Q9C0K1	Metal cation symporter ZIP8	gencc,clinvar
SCAF4	HGNC:19304	ENSG00000156304	O95104	SR-related and CTD-associated factor 4	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC39A8	Metal cation symporter ZIP8	Electroneutral divalent metal cation:bicarbonate symporter of the plasma membrane mediating the cellular uptake of zinc and manganese, two divalent metal cations important for development, tissue homeostasis and immunity.
SCAF4	SR-related and CTD-associated factor 4	Anti-terminator protein required to prevent early mRNA termination during transcription.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Transporter	1	38.9×	0.051
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC39A8	Transporter	yes		ZIP, ZIP_Transporter
SCAF4	Other/Unknown	no		RRM_dom, CID_dom, ENTH_VHS

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
lower lobe of lung	1
parotid gland	1
visceral pleura	1
buccal mucosa cell	1
sperm	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC39A8	269	ubiquitous	marker	parotid gland, lower lobe of lung, visceral pleura
SCAF4	267	ubiquitous	marker	tendon of biceps brachii, buccal mucosa cell, sperm

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SCAF4	2,068
SLC39A8	1,364

Structural data

PDB: 1 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SCAF4	O95104	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SLC39A8	Q9C0K1	73.46

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. 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
Zinc transporters	1	1142.0×	0.003	SLC39A8
Zinc influx into cells by the SLC39 gene family	1	1142.0×	0.003	SLC39A8
Metal ion SLC transporters	1	601.0×	0.003	SLC39A8
R-HSA-425366	1	181.3×	0.008	SLC39A8
SLC-mediated transmembrane transport	1	59.2×	0.020	SLC39A8
Transport of small molecules	1	25.1×	0.040	SLC39A8

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
leukocyte adhesion to arterial endothelial cell	1	8426.0×	0.001	SLC39A8
plasma membrane selenite transport	1	8426.0×	0.001	SLC39A8
mitochondrial manganese ion transmembrane transport	1	8426.0×	0.001	SLC39A8
mercury ion transport	1	4213.0×	0.001	SLC39A8
iron ion import across plasma membrane	1	4213.0×	0.001	SLC39A8
negative regulation of termination of RNA polymerase II transcription, poly(A)-coupled	1	4213.0×	0.001	SCAF4
manganese ion transmembrane transport	1	2808.7×	0.001	SLC39A8
cellular detoxification of cadmium ion	1	2808.7×	0.001	SLC39A8
intracellular manganese ion homeostasis	1	1685.2×	0.001	SLC39A8
cadmium ion transmembrane transport	1	1685.2×	0.001	SLC39A8
cartilage homeostasis	1	1685.2×	0.001	SLC39A8
arginine metabolic process	1	1203.7×	0.002	SLC39A8
cobalt ion transport	1	1203.7×	0.002	SLC39A8
zinc ion import across plasma membrane	1	842.6×	0.002	SLC39A8
zinc ion transport	1	766.0×	0.002	SLC39A8
intracellular monoatomic cation homeostasis	1	561.7×	0.003	SLC39A8
bicarbonate transport	1	401.2×	0.004	SLC39A8
zinc ion transmembrane transport	1	351.1×	0.004	SLC39A8
intracellular zinc ion homeostasis	1	240.7×	0.006	SLC39A8
protein N-linked glycosylation	1	131.7×	0.010	SLC39A8
regulation of membrane potential	1	115.4×	0.010	SLC39A8
DNA-templated transcription	1	112.3×	0.010	SLC39A8
negative regulation of canonical NF-kappaB signal transduction	1	86.0×	0.013	SLC39A8
negative regulation of inflammatory response	1	68.5×	0.016	SLC39A8
extracellular matrix organization	1	61.1×	0.017	SLC39A8
regulation of DNA-templated transcription	1	15.8×	0.062	SLC39A8

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
SLC39A8	0	0
SCAF4	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	1	SLC39A8
E	Difficult family or no structure, no drug	1	SCAF4

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)
SLC39A8	0	—
SCAF4	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.