Agammaglobulinemia 9, autosomal recessive

Summary

Agammaglobulinemia 9, autosomal recessive (MONDO:0030519) is a disease caused by SLC39A7 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: SLC39A7 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 9

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	agammaglobulinemia 9, autosomal recessive
Mondo ID	MONDO:0030519
OMIM	619693
Orphanet	693627
DOID	DOID:0081141
UMLS	C5562059
MedGen	1794269
GARD	0025591
Is cancer (heuristic)	no

Also known as: AGM9

Data availability: 9 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › immune system disorder › inborn error of immunity › B cell deficiency › agammaglobulinemia › agammaglobulinemia 9, autosomal recessive

Related subtypes (9): congenital agammaglobulinemia, immunodeficiency 61, Good syndrome, isolated agammaglobulinemia, syndromic agammaglobulinemia, activated PI3K-delta syndrome, agammaglobulinemia 10, autosomal dominant, agammaglobulinemia, autosomal recessive, due to BOB1 deficiency, agammaglobulinemia 8b, autosomal recessive

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

9 retrieved; paginated sample, class counts are floors:

4 uncertain significance, 3 pathogenic, 2 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1333089	NM_006979.3(SLC39A7):c.1087G>A (p.Glu363Lys)	SLC39A7	Pathogenic	no assertion criteria provided
1333090	NM_006979.3(SLC39A7):c.650T>C (p.Leu217Pro)	SLC39A7	Pathogenic	criteria provided, single submitter
1507871	NM_006979.3(SLC39A7):c.568C>G (p.Pro190Ala)	SLC39A7	Pathogenic	criteria provided, single submitter
1333091	NM_006979.3(SLC39A7):c.1114C>T (p.Gln372Ter)	SLC39A7	Likely pathogenic	criteria provided, single submitter
3065745	NM_006979.3(SLC39A7):c.868C>T (p.Arg290Ter)	SLC39A7	Likely pathogenic	criteria provided, single submitter
1333092	NM_006979.3(SLC39A7):c.1184C>T (p.Thr395Ile)	SLC39A7	Uncertain significance	criteria provided, single submitter
2171639	NM_006979.3(SLC39A7):c.176_199dup (p.His66_Thr67insSerHisAlaHisGlyHisGlyHis)	SLC39A7	Uncertain significance	criteria provided, multiple submitters, no conflicts
2584820	NM_006979.3(SLC39A7):c.1291G>A (p.Ala431Thr)	SLC39A7	Uncertain significance	criteria provided, single submitter
4080083	NM_006979.3(SLC39A7):c.180T>A (p.His60Gln)	SLC39A7	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 1 · 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
SLC39A7	Strong	Autosomal recessive	agammaglobulinemia 9, autosomal recessive	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC39A7	Orphanet:693627	Agammaglobulinemia-skin involvement-failure to thrive syndrome

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SLC39A7	HGNC:4927	ENSG00000112473	Q92504	Zinc transporter SLC39A7	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC39A7	Zinc transporter SLC39A7	Transports Zn(2+) from the endoplasmic reticulum (ER)/Golgi apparatus to the cytosol, playing an essential role in the regulation of cytosolic zinc levels.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC39A7	Other/Unknown	no		ZIP

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
body of pancreas	1
islet of Langerhans	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC39A7	133	ubiquitous	marker	stromal cell of endometrium, islet of Langerhans, body of pancreas

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLC39A7	1,679

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SLC39A7	Q92504	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. Enrichment computed across 1 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	SLC39A7
Zinc influx into cells by the SLC39 gene family	1	1142.0×	0.003	SLC39A7
Metal ion SLC transporters	1	601.0×	0.003	SLC39A7
R-HSA-425366	1	181.3×	0.008	SLC39A7
SLC-mediated transmembrane transport	1	59.2×	0.020	SLC39A7
Transport of small molecules	1	25.1×	0.040	SLC39A7

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of ferroptosis	1	16852.0×	3e-04	SLC39A7
skin epidermis development	1	4213.0×	6e-04	SLC39A7
zinc ion transmembrane transport	1	702.2×	0.002	SLC39A7
intracellular zinc ion homeostasis	1	481.5×	0.003	SLC39A7
B cell differentiation	1	218.9×	0.005	SLC39A7

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SLC39A7	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
SLC39A7	2	Binding:1, Functional:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; 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	1	SLC39A7

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SLC39A7	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.