Atransferrinemia

Summary

Atransferrinemia (MONDO:0008846) is a disease caused by TF (GenCC Strong), with 1 cohort gene and 1 clinical trial.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: TF (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 78
• Phenotypes (HPO): 6
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		16	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

6 HPO clinical features (Orphanet curated; top 6 by frequency):

HPO ID	Term	Frequency
HP:0001903	Anemia	Very frequent (80-99%)
HP:0002719	Recurrent infections	Frequent (30-79%)
HP:0000821	Hypothyroidism	Occasional (5-29%)
HP:0001369	Arthritis	Occasional (5-29%)
HP:0001626	Abnormality of the cardiovascular system	Occasional (5-29%)
HP:0001732	Abnormality of the pancreas	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	atransferrinemia
Mondo ID	MONDO:0008846
MeSH	C538259
OMIM	209300
Orphanet	1195
DOID	DOID:0050649
NCIT	C125693
SNOMED CT	111571009
UMLS	C0521802
MedGen	105489
GARD	0009595
NORD	819
Is cancer (heuristic)	no

Also known as: atransferrinemia · congenital atransferrinemia · congenital hypotransferrinemia · familial hypotransferrinemia · hereditary atransferrinemia

Data availability: 78 ClinVar variants · 5 GenCC gene-disease records · 1 cell line.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › inborn metal metabolism disorder › atransferrinemia

Related subtypes (8): familial periodic paralysis, hereditary hemochromatosis, acrodermatitis enteropathica, Wilson disease, Menkes disease, familial primary hypomagnesemia, pseudohypoparathyroidism, sulfite oxidase deficiency due to molybdenum cofactor deficiency

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

78 retrieved; paginated sample, class counts are floors:

24 uncertain significance, 16 benign, 13 conflicting classifications of pathogenicity, 12 likely pathogenic, 6 benign/likely benign, 4 likely benign, 3 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
12619	NM_001063.4(TF):c.562_564delinsAA (p.Gln188fs)	TF	Pathogenic	no assertion criteria provided
12620	NM_001063.4(TF):c.1429G>C (p.Ala477Pro)	TF	Pathogenic	no assertion criteria provided
12621	NM_001063.4(TF):c.229G>A (p.Asp77Asn)	TF	Pathogenic	no assertion criteria provided
1699991	NM_001063.4(TF):c.1444C>T (p.Pro482Ser)	TF	Likely pathogenic	no assertion criteria provided
218294	NM_001063.4(TF):c.1825C>T (p.Arg609Trp)	TF	Likely pathogenic	criteria provided, single submitter
3588594	NM_001063.4(TF):c.147del (p.Pro50fs)	TF	Likely pathogenic	criteria provided, single submitter
3588595	NM_001063.4(TF):c.216+2T>C	TF	Likely pathogenic	criteria provided, single submitter
3588596	NM_001063.4(TF):c.325+1G>A	TF	Likely pathogenic	criteria provided, single submitter
3588597	NM_001063.4(TF):c.394C>T (p.Arg132Ter)	TF	Likely pathogenic	criteria provided, single submitter
3588598	NM_001063.4(TF):c.440G>A (p.Trp147Ter)	TF	Likely pathogenic	criteria provided, single submitter
3588599	NM_001063.4(TF):c.817C>T (p.Arg273Ter)	TF	Likely pathogenic	criteria provided, single submitter
3588600	NM_001063.4(TF):c.1007_1008del (p.Gly335_Tyr336insTer)	TF	Likely pathogenic	criteria provided, single submitter
3588601	NM_001063.4(TF):c.1088G>A (p.Trp363Ter)	TF	Likely pathogenic	criteria provided, single submitter
3588602	NM_001063.4(TF):c.1872+1G>C	TF	Likely pathogenic	criteria provided, single submitter
4278393	NM_001063.4(TF):c.923dup (p.His308fs)	TF	Likely pathogenic	criteria provided, single submitter
343423	NM_001063.4(TF):c.60C>T (p.Val20=)	TF	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
343424	NM_001063.4(TF):c.119G>A (p.Ser40Asn)	TF	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
343428	NM_001063.4(TF):c.228G>A (p.Ala76=)	TF	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
343435	NM_001063.4(TF):c.585G>A (p.Gly195=)	TF	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
343442	NM_001063.4(TF):c.1107C>T (p.His369=)	TF	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
343449	NM_001063.4(TF):c.1785C>T (p.Asn595=)	TF	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
730768	NM_001063.4(TF):c.1095G>A (p.Ala365=)	TF	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
735968	NM_001063.4(TF):c.43+8C>A	TF	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
763909	NM_001063.4(TF):c.1029G>A (p.Arg343=)	TF	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
900554	NM_001063.4(TF):c.828C>T (p.Gly276=)	TF	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
900555	NM_001063.4(TF):c.1027C>T (p.Arg343Trp)	TF	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
902238	NM_001063.4(TF):c.1204-14C>A	TF	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
903055	NM_001063.4(TF):c.502+12G>A	TF	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1174118	NM_001063.4(TF):c.2063-11_2063-10del	TF	Uncertain significance	criteria provided, single submitter
12623	NM_001063.4(TF):c.1180G>A (p.Glu394Lys)	TF	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
TF	Strong	Autosomal recessive	atransferrinemia	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TF	Orphanet:1195	Congenital atransferrinemia

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
TF	HGNC:11740	ENSG00000091513	P02787	Serotransferrin	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TF	Serotransferrin	Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate.

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)
TF	Other/Unknown	no		Transferrin-like_dom, Transferrin, Transferrin_Fe_BS

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
corpus callosum	1
inferior vagus X ganglion	1
medulla oblongata	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TF	249	broad	marker	inferior vagus X ganglion, medulla oblongata, corpus callosum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TF	2,217

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TF	P02787	66

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. 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
Transferrin endocytosis and recycling	1	368.4×	0.010	TF
Iron uptake and transport	1	346.1×	0.010	TF
Cargo recognition for clathrin-mediated endocytosis	1	104.8×	0.012	TF
Post-translational protein phosphorylation	1	100.2×	0.012	TF
Platelet degranulation	1	87.8×	0.012	TF
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	1	86.5×	0.012	TF
Clathrin-mediated endocytosis	1	85.2×	0.012	TF

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
cellular response to iron ion	1	2407.4×	0.004	TF
iron ion transport	1	887.0×	0.004	TF
positive regulation of receptor-mediated endocytosis	1	802.5×	0.004	TF
multicellular organismal-level iron ion homeostasis	1	581.1×	0.004	TF
osteoclast differentiation	1	343.9×	0.005	TF
antibacterial humoral response	1	330.4×	0.005	TF
intracellular iron ion homeostasis	1	244.2×	0.006	TF
positive regulation of proteasomal ubiquitin-dependent protein catabolic process	1	210.7×	0.006	TF
regulation of protein stability	1	125.8×	0.009	TF
cell surface receptor signaling pathway	1	64.1×	0.016	TF

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
TF	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
TF	22	Binding:13, Functional:9

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	TF

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)
TF	22	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01797055	PHASE2	ACTIVE_NOT_RECRUITING	Apotransferrin in Atransferrinemia