AMN

Summary

AMN (amnion associated transmembrane protein, HGNC:14604) is a protein-coding gene on chromosome 14q32.32, encoding Protein amnionless (Q9BXJ7). Membrane-bound component of the endocytic receptor formed by AMN and CUBN.

The protein encoded by this gene is a type I transmembrane protein. It is thought to modulate bone morphogenetic protein (BMP) receptor function by serving as an accessory or coreceptor, and thus facilitates or hinders BMP binding. It is known that the mouse AMN gene is expressed in the extraembryonic visceral endoderm layer during gastrulation, but it is found to be mutated in amnionless mouse. The encoded protein has sequence similarity to short gastrulation (Sog) and procollagen IIA proteins in Drosophila.

Source: NCBI Gene 81693 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Imerslund-Grasbeck syndrome type 1 (Strong, GenCC) — +2 more curated relationships
• Clinical variants (ClinVar): 715 total — 35 pathogenic, 40 likely-pathogenic
• Phenotypes (HPO): 39
• MANE Select transcript: NM_030943

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14604
Approved symbol	AMN
Name	amnion associated transmembrane protein
Location	14q32.32
Locus type	gene with protein product
Status	Approved
Aliases	amnionless
Ensembl gene	ENSG00000166126
Ensembl biotype	protein_coding
OMIM	605799
Entrez	81693

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 4 protein_coding, 4 retained_intron

ENST00000299155, ENST00000541086, ENST00000558590, ENST00000559442, ENST00000559507, ENST00000559525, ENST00000559789, ENST00000872999

RefSeq mRNA: 2 — MANE Select: NM_030943 NM_001425246, NM_030943

CCDS: CCDS9977

Canonical transcript exons

ENST00000299155 — 12 exons

Exon	Start	End
ENSE00001100065	102923711	102923829
ENSE00001152389	102922663	102922731
ENSE00001185522	102930576	102930842
ENSE00003461160	102930165	102930327
ENSE00003508474	102928426	102928513
ENSE00003533696	102929428	102929536
ENSE00003545904	102929924	102930086
ENSE00003558403	102930406	102930493
ENSE00003633578	102929121	102929258
ENSE00003658991	102923935	102923979
ENSE00003672950	102928758	102928975
ENSE00003688625	102929655	102929737

Expression profiles

Bgee: expression breadth ubiquitous, 223 present calls, max score 98.90.

FANTOM5 (CAGE): breadth broad, TPM avg 1.5328 / max 319.0321, expressed in 283 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
141682	0.7742	65
141687	0.6845	235
141684	0.0387	13
141685	0.0249	12
141683	0.0105	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	98.90	gold quality
jejunal mucosa	UBERON:0000399	93.98	gold quality
duodenum	UBERON:0002114	93.53	gold quality
right lobe of liver	UBERON:0001114	93.19	gold quality
small intestine Peyer’s patch	UBERON:0003454	92.77	gold quality
type B pancreatic cell	CL:0000169	91.70	gold quality
small intestine	UBERON:0002108	91.59	gold quality
lower esophagus mucosa	UBERON:0035834	90.08	gold quality
vena cava	UBERON:0004087	89.93	silver quality
transverse colon	UBERON:0001157	89.57	gold quality
olfactory bulb	UBERON:0002264	89.55	gold quality
adult mammalian kidney	UBERON:0000082	89.35	gold quality
jejunum	UBERON:0002115	86.73	gold quality
colonic mucosa	UBERON:0000317	86.21	gold quality
liver	UBERON:0002107	86.10	gold quality
metanephros cortex	UBERON:0010533	85.49	gold quality
mucosa of sigmoid colon	UBERON:0004993	85.39	gold quality
tongue squamous epithelium	UBERON:0006919	85.02	silver quality
esophagus mucosa	UBERON:0002469	84.26	gold quality
body of tongue	UBERON:0011876	83.50	silver quality
pancreatic ductal cell	CL:0002079	83.29	silver quality
right uterine tube	UBERON:0001302	82.93	gold quality
kidney	UBERON:0002113	82.86	gold quality
lateral nuclear group of thalamus	UBERON:0002736	82.82	silver quality
ileal mucosa	UBERON:0000331	82.72	silver quality
gluteal muscle	UBERON:0002000	82.30	gold quality
parotid gland	UBERON:0001831	81.65	silver quality
pylorus	UBERON:0001166	81.64	gold quality
pons	UBERON:0000988	81.39	gold quality
cortex of kidney	UBERON:0001225	81.07	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-MTAB-9906	yes	1101.25
E-GEOD-114530	yes	515.51
E-GEOD-125970	yes	80.16
E-CURD-114	yes	45.07
E-ANND-3	yes	13.63
E-MTAB-8410	yes	11.59
E-MTAB-9388	yes	11.10
E-HCAD-38	no	439.42

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 11)

• homozygous mutations affecting exons 1-4 of human AMN lead to megaloblastic anemia 1 (PMID:12590260)
• cubilin and amnionless are subunits of a novel cubilin/amnionless (cubam) complex (PMID:14576052)
• Recurrent spontaneous abortions may be caused by mutations in the Amnionless gene. (PMID:16403802)
• This review summarizes recent data on the biological function of amnionless and focuses on its implication in embryonic nutrition and central nervous system malformations. (PMID:17979745)
• amnionless is essential for the correct luminal expression of cubilin in humans. (PMID:21750092)
• We present evidence that this founder mutation causes over 50% of the Imerslund-Grasbeck syndrome (IGS) cases among Arabic, Turkish, and Sephardic Jewish families, and the mutation is as old as human civvlization. (PMID:22078000)
• Our genetic screening of 154 families of patients with inherited cobalamin malabsorption revealed population-specific mutations, mutational hotspots, and functionally distinct regions in the three causal genes: CUBN, AMN, and GIF. (PMID:22929189)
• heterozygous mutations in AMN in a family from the United Kingdom with clinical features of Imerslund-Grasbeck Syndrome (PMID:26040326)
• Study shows that cubilin mutations (novel and some previously reported) and all previously reported amnionless missense mutations resulted in endoplasmic reticulum retention and completely inhibited amnionless-dependent plasma membrane expression of cubilin. (PMID:29402915)
• Data indicate the crystal structure of amnionless (AMN) in complex with the amino-terminal region of intrinsic factor-cobalamin receptor (cubilin). (PMID:30523278)
• Imerslund-Grasbeck Syndrome presenting with microangiopathic hemolytic anemia in a child. (PMID:32045704)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	amn	ENSDARG00000062947
mus_musculus	Amn	ENSMUSG00000021278
rattus_norvegicus	Amn	ENSRNOG00000009050
drosophila_melanogaster	Amnionless	FBGN0025686

Protein

Protein identifiers

Protein amnionless — Q9BXJ7 (reviewed: Q9BXJ7)

All UniProt accessions (3): Q9BXJ7, H0YKJ5, H0YMX8

UniProt curated annotations — full annotation on UniProt →

Function. Membrane-bound component of the endocytic receptor formed by AMN and CUBN. Required for normal CUBN glycosylation and trafficking to the cell surface. The complex formed by AMN and CUBN is required for efficient absorption of vitamin B12. Required for normal CUBN-mediated protein transport in the kidney.

Subunit / interactions. Interacts (via extracellular region) with CUBN/cubilin, giving rise to a huge complex containing one AMN chain and three CUBN chains.

Subcellular location. Apical cell membrane. Cell membrane. Endosome membrane. Membrane. Coated pit Secreted.

Tissue specificity. Detected in proximal tubules in the kidney cortex (at protein level). Long isoforms are highly expressed in small intestine, colon and kidney (renal proximal tubule epithelial cells). Shorter isoforms are detected at lower levels in testis, thymus and peripheral blood leukocytes.

Post-translational modifications. N-glycosylated. A soluble form arises by proteolytic removal of the membrane anchor.

Disease relevance. Imerslund-Grasbeck syndrome 2 (IGS2) [MIM:618882] A form of Imerslund-Grasbeck syndrome, a rare autosomal recessive disorder characterized by vitamin B12 deficiency commonly resulting in megaloblastic anemia, which is responsive to parenteral vitamin B12 therapy and appears in infancy or early childhood. Clinical manifestations include failure to thrive, infections and neurological damage. Mild proteinuria, with no signs of kidney disease, is present in about half of the patients. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The complex formed by AMN and CUBN is composed of a 400 Angstrom long stem and a globular crown region. The stem region is probably formed by AMN and the CUBN N-terminal region, including the EGF-like domains. The crown is probably formed by the CUBN CUB domains.

Miscellaneous. The role of Amn in embryonic development seems to be species specific. In mice, null mutations lead to embryonic lethality. Human mutations give rise to much milder symptoms.

Isoforms (1)

UniProt ID	Names	Canonical?
Q9BXJ7-1	1	yes

RefSeq proteins (2): NP_001412175, NP_112205* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026112	AMN	Family

Pfam: PF14828

UniProt features (55 total): strand 18, helix 11, disulfide bond 6, mutagenesis site 4, sequence variant 3, turn 3, chain 2, topological domain 2, signal peptide 1, sequence conflict 1, transmembrane region 1, domain 1, region of interest 1, glycosylation site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6GJE	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BXJ7-F1	80.78	0.61

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (6): 137–213, 205–211, 223–249, 234–250, 239–253, 43–96

Glycosylation sites (1): 35

Mutagenesis-validated functional residues (4):

Position	Phenotype
35	loss of expression at the cell membrane.
37	no effect.
59	loss of interaction with cubn and strongly reduced cubn expression at the cell surface.
254	loss of interaction with cubn and strongly reduced cubn expression at the cell surface.

Function

Pathways and Gene Ontology

Reactome pathways

15 pathways

ID	Pathway
R-HSA-3359462	Defective AMN causes MGA1
R-HSA-3359463	Defective CUBN causes MGA1
R-HSA-8964011	HDL clearance
R-HSA-9758881	Uptake of dietary cobalamins into enterocytes
R-HSA-1430728	Metabolism
R-HSA-1643685	Disease
R-HSA-174824	Plasma lipoprotein assembly, remodeling, and clearance
R-HSA-196741	Cobalamin (Cbl, vitamin B12) transport and metabolism
R-HSA-196849	Metabolism of water-soluble vitamins and cofactors
R-HSA-196854	Metabolism of vitamins and cofactors
R-HSA-3296469	Defects in cobalamin (B12) metabolism
R-HSA-3296482	Defects in vitamin and cofactor metabolism
R-HSA-382551	Transport of small molecules
R-HSA-5668914	Diseases of metabolism
R-HSA-8964043	Plasma lipoprotein clearance

MSigDB gene sets: 195 (showing top): BENPORATH_ES_WITH_H3K27ME3, SCHLESINGER_METHYLATED_DE_NOVO_IN_CANCER, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, GOBP_GOLGI_TO_PLASMA_MEMBRANE_TRANSPORT, GOBP_COBALAMIN_METABOLIC_PROCESS, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_MEMBRANE, GOBP_TETRAPYRROLE_METABOLIC_PROCESS, GOBP_GOLGI_TO_PLASMA_MEMBRANE_PROTEIN_TRANSPORT, GOBP_VITAMIN_TRANSPORT, GOCC_APICAL_PLASMA_MEMBRANE, GOBP_RENAL_ABSORPTION, GOMF_SIGNALING_RECEPTOR_BINDING, GOBP_LOCALIZATION_WITHIN_MEMBRANE, GOBP_IMPORT_INTO_CELL

GO Biological Process (7): receptor-mediated endocytosis (GO:0006898), intracellular protein localization (GO:0008104), cobalamin metabolic process (GO:0009235), cobalamin transport (GO:0015889), Golgi to plasma membrane protein transport (GO:0043001), renal protein absorption (GO:0097017), protein transport (GO:0015031)

GO Molecular Function (3): signaling receptor binding (GO:0005102), cargo receptor activity (GO:0038024), protein binding (GO:0005515)

GO Cellular Component (15): obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), clathrin-coated pit (GO:0005905), endosome membrane (GO:0010008), membrane (GO:0016020), apical plasma membrane (GO:0016324), endocytic vesicle (GO:0030139), brush border membrane (GO:0031526), microvillus membrane (GO:0031528), signaling receptor complex (GO:0043235), extracellular exosome (GO:0070062), extracellular region (GO:0005576), endosome (GO:0005768), protein-containing complex (GO:0032991), apical part of cell (GO:0045177)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
Defects in cobalamin (B12) metabolism	2
Plasma lipoprotein clearance	1
Cobalamin (Cbl, vitamin B12) transport and metabolism	1
Transport of small molecules	1
Metabolism of water-soluble vitamins and cofactors	1
Metabolism of vitamins and cofactors	1
Metabolism	1
Defects in vitamin and cofactor metabolism	1
Diseases of metabolism	1
Disease	1
Plasma lipoprotein assembly, remodeling, and clearance	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
membrane	2
endomembrane system	2
cytoplasmic vesicle	2
cell projection membrane	2
endocytosis	1
macromolecule localization	1
tetrapyrrole metabolic process	1
vitamin transport	1
nitrogen compound transport	1
Golgi to plasma membrane transport	1
protein transport	1
establishment of protein localization to plasma membrane	1
protein localization to plasma membrane	1
renal absorption	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
protein binding	1
molecular_function	1
vesicle-mediated transport	1
molecular adaptor activity	1
binding	1
cell periphery	1
endosome	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
apical part of cell	1
plasma membrane region	1
brush border	1
apical plasma membrane	1
microvillus	1
protein-containing complex	1
extracellular vesicle	1
cellular_component	1

Protein interactions and networks

STRING

408 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AMN	CUBN	O60494	999
AMN	LRP2	P98164	998
AMN	CBLIF	P27352	899
AMN	TCN2	P20062	765
AMN	DAB2	P98082	758
AMN	C1R	P00736	691
AMN	C1S	P09871	652
AMN	ALB	P02768	632
AMN	BMP1	P13497	612
AMN	CDC42BPB	Q9Y5S2	608
AMN	APOA1	P02647	593
AMN	TCN1	P20061	584
AMN	CHRD	Q9H2X0	583
AMN	GC	P02774	571
AMN	CBL	P22681	566

IntAct

5 interactions, top by confidence:

A	B	Type	Score
AMN	CUBN	psi-mi:“MI:0407”(direct interaction)	0.600
AMN	CUBN	psi-mi:“MI:0915”(physical association)	0.600
AMN	STAMBP	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (1): AMN (Two-hybrid)

ESM2 similar proteins: A0A5F4BST2, A0PJX4, A0RZB4, A1L515, A2A9Q0, A2BDG0, A6QQ85, A6XN32, A9JSM3, B0FP48, D3YZZ2, D4A2Q0, E5RIL1, F1SAM7, P01183, Q1RMK9, Q3UPR0, Q3ZCQ3, Q5BIV7, Q5BIV9, Q5BK01, Q5GH56, Q5GH64, Q5GH72, Q5SNT2, Q5T7M4, Q6IEE6, Q6PRD1, Q6UWJ8, Q70RD5, Q864V4, Q86UD0, Q8BWU1, Q8BX43, Q8CCB5, Q8IVY1, Q8K064, Q8K2Y3, Q8K5A9, Q8N9H8

Diamond homologs: F1SAM7, Q6UKI2, Q99JB7, Q9BXJ7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	35
Likely pathogenic	40
Uncertain significance	189
Likely benign	399
Benign	24

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1323130	NM_030943.4(AMN):c.297_299delinsAG (p.Glu100fs)	Pathogenic
1879782	NM_030943.4(AMN):c.493dup (p.Ser165fs)	Pathogenic
2429110	NC_000014.9:g.102573453_103575949del	Pathogenic
2701902	NM_030943.4(AMN):c.170C>G (p.Ser57Ter)	Pathogenic
2702738	NM_030943.4(AMN):c.968_975del (p.Arg323fs)	Pathogenic
2707269	NM_030943.4(AMN):c.587del (p.Gly196fs)	Pathogenic
2738292	NM_030943.4(AMN):c.683_705dup (p.Gln236fs)	Pathogenic
2770763	NM_030943.4(AMN):c.534_535dup (p.Leu179fs)	Pathogenic
2771124	NM_030943.4(AMN):c.669C>A (p.Cys223Ter)	Pathogenic
2831212	NM_030943.4(AMN):c.58del (p.Val20fs)	Pathogenic
2831451	NM_030943.4(AMN):c.545del (p.Phe182fs)	Pathogenic
2839426	NM_030943.4(AMN):c.1114dup (p.Ala372fs)	Pathogenic
2862251	NM_030943.4(AMN):c.73del (p.Val25fs)	Pathogenic
2896512	NM_030943.4(AMN):c.78del (p.Asn27fs)	Pathogenic
2902916	NM_030943.4(AMN):c.1255dup (p.Leu419fs)	Pathogenic
2908530	NM_030943.4(AMN):c.411C>A (p.Cys137Ter)	Pathogenic
2993998	NM_030943.4(AMN):c.890C>A (p.Ser297Ter)	Pathogenic
3003642	NM_030943.4(AMN):c.862C>T (p.Gln288Ter)	Pathogenic
3011943	NM_030943.4(AMN):c.1161dup (p.Arg388fs)	Pathogenic
3012147	NM_030943.4(AMN):c.34C>T (p.Gln12Ter)	Pathogenic
3066362	NM_030943.4(AMN):c.682C>T (p.Gln228Ter)	Pathogenic
3243968	NC_000014.8:g.(?103389228)(103394842_?)del	Pathogenic
395243	GRCh37/hg19 14q32.32-32.33(chr14:103390060-104436909)x1	Pathogenic
4726084	NM_030943.4(AMN):c.442_445dup (p.Ser149fs)	Pathogenic
523538	NM_030943.4(AMN):c.320_321dup (p.Asp108fs)	Pathogenic
532214	NC_000014.9:g.(?102870182)(102930700_?)del	Pathogenic
56749	NM_030943.4(AMN):c.14del (p.Gly5fs)	Pathogenic
56751	NM_030943.4(AMN):c.208-2A>G	Pathogenic
56756	NM_030943.4(AMN):c.663G>A (p.Trp221Ter)	Pathogenic
56759	NM_030943.4(AMN):c.742C>T (p.Gln248Ter)	Pathogenic

SpliceAI

1850 predictions. Top by Δscore:

Variant	Effect	Δscore
14:102929765:G:GT	donor_gain	1.0000
14:102929765:G:T	donor_gain	1.0000
14:102929800:G:GT	donor_gain	1.0000
14:102930325:CAGGT:C	donor_loss	1.0000
14:102930327:GGTA:G	donor_loss	1.0000
14:102930328:G:GC	donor_loss	1.0000
14:102930329:T:G	donor_loss	1.0000
14:102923738:G:A	acceptor_gain	0.9900
14:102928510:GCGG:G	donor_gain	0.9900
14:102928513:GGTGA:G	donor_loss	0.9900
14:102928514:G:GC	donor_loss	0.9900
14:102928515:T:G	donor_loss	0.9900
14:102928777:C:CA	acceptor_gain	0.9900
14:102928801:T:G	acceptor_gain	0.9900
14:102929086:C:CA	acceptor_gain	0.9900
14:102929087:G:A	acceptor_gain	0.9900
14:102929091:T:TA	acceptor_gain	0.9900
14:102929256:G:GT	donor_gain	0.9900
14:102929256:GAGG:G	donor_loss	0.9900
14:102929257:AGGT:A	donor_loss	0.9900
14:102929258:GGTG:G	donor_loss	0.9900
14:102929260:T:A	donor_loss	0.9900
14:102929651:GCAGG:G	acceptor_loss	0.9900
14:102929652:CAGGA:C	acceptor_loss	0.9900
14:102929653:A:AG	acceptor_gain	0.9900
14:102929654:G:GA	acceptor_gain	0.9900
14:102929654:GGA:G	acceptor_gain	0.9900
14:102929733:GTCTG:G	donor_gain	0.9900
14:102929759:C:G	donor_gain	0.9900
14:102929919:CCCA:C	acceptor_loss	0.9900

AlphaMissense

2867 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:102923775:G:C	W36C	0.997
14:102923775:G:T	W36C	0.997
14:102928816:G:C	W118C	0.995
14:102928816:G:T	W118C	0.995
14:102928798:G:C	W112C	0.991
14:102928798:G:T	W112C	0.991
14:102923739:G:C	W24C	0.990
14:102923739:G:T	W24C	0.990
14:102928796:T:A	W112R	0.988
14:102928796:T:C	W112R	0.988
14:102923773:T:A	W36R	0.987
14:102923773:T:C	W36R	0.987
14:102928773:T:G	F104C	0.986
14:102928814:T:A	W118R	0.986
14:102928814:T:C	W118R	0.986
14:102928910:T:C	F150L	0.986
14:102928912:C:A	F150L	0.986
14:102928912:C:G	F150L	0.986
14:102923816:T:C	F50S	0.984
14:102923816:T:G	F50C	0.984
14:102929182:T:C	F192S	0.984
14:102928772:T:C	F104L	0.982
14:102928774:C:A	F104L	0.982
14:102928774:C:G	F104L	0.982
14:102923737:T:A	W24R	0.981
14:102923737:T:C	W24R	0.981
14:102929687:T:C	F265L	0.981
14:102929689:T:A	F265L	0.981
14:102929689:T:G	F265L	0.981
14:102928869:C:A	P136H	0.978

dbSNP variants (sampled 300 via entrez): RS1000070117 (14:102922228 A>C,G), RS1000562850 (14:102924484 G>A), RS1001167759 (14:102926255 T>C), RS1002128045 (14:102922977 C>A,G), RS1002202412 (14:102922082 C>T), RS1002565215 (14:102926380 G>A,C), RS1002802601 (14:102920818 TCACCATC>T,TCACCATCCACCATC), RS1003119258 (14:102931300 G>A), RS1003541193 (14:102928032 C>T), RS1003560283 (14:102930574 A>G), RS1003572232 (14:102927637 C>A,T), RS1003920333 (14:102928694 C>T), RS1004249628 (14:102928895 C>T), RS1004568760 (14:102926614 T>C), RS1004857882 (14:102930158 G>A,T)

Disease associations

OMIM: gene MIM:605799 | disease phenotypes: MIM:261100, MIM:618882, MIM:619061, MIM:614228

GenCC curated gene-disease

Disease	Classification	Inheritance
Imerslund-Grasbeck syndrome type 1	Strong	Autosomal recessive
Imerslund-Grasbeck syndrome type 2	Strong	Autosomal recessive
Imerslund-Grasbeck syndrome	Supportive	Autosomal recessive

Mondo (7): Imerslund-Grasbeck syndrome (MONDO:0009853), Imerslund-Grasbeck syndrome type 1 (MONDO:0100156), Imerslund-Grasbeck syndrome type 2 (MONDO:0100157), mitochondrial complex IV deficiency, nuclear type 17 (MONDO:0033652), Charcot-Marie-Tooth disease axonal type 2O (MONDO:0013644), megaloblastic anemia (MONDO:0001700), vitamin B12 deficiency (MONDO:0020696)

Orphanet (2): Imerslund-Gräsbeck syndrome (Orphanet:35858), Autosomal dominant Charcot-Marie-Tooth disease type 2O (Orphanet:284232)

HPO phenotypes

39 total (30 of 39 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000083	Renal insufficiency
HP:0000093	Proteinuria
HP:0000206	Glossitis
HP:0000707	Abnormality of the nervous system
HP:0000750	Delayed speech and language development
HP:0000980	Pallor
HP:0001252	Hypotonia
HP:0001508	Failure to thrive
HP:0001510	Growth delay
HP:0001649	Tachycardia
HP:0001824	Weight loss
HP:0001873	Thrombocytopenia
HP:0001875	Decreased total neutrophil count
HP:0001876	Pancytopenia
HP:0001889	Megaloblastic anemia
HP:0001892	Abnormal bleeding
HP:0001903	Anemia
HP:0001923	Reticulocytosis
HP:0001972	Macrocytic anemia
HP:0002013	Vomiting
HP:0002014	Diarrhea
HP:0002019	Constipation
HP:0002376	Developmental regression
HP:0002721	Immunodeficiency
HP:0004396	Poor appetite
HP:0004821	Hypersegmentation of neutrophil nuclei
HP:0004823	Anisopoikilocytosis
HP:0008454	Lumbar kyphosis

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D014806	Vitamin B 12 Deficiency	C18.654.521.500.133.699.923
C538556	Imerslund-Grasbeck syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases methylation	2
Valproic Acid	affects methylation, decreases expression, increases methylation	2
aristolochic acid I	increases expression	1
dicrotophos	decreases expression	1
perfluorooctanoic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
obeticholic acid	decreases expression	1
abrine	increases expression	1
Acetaminophen	decreases expression	1
Cadmium	increases abundance, increases expression	1
Cisplatin	decreases reaction, increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Estradiol	affects cotreatment, decreases expression	1
Folic Acid	decreases expression	1
Lead	decreases expression	1
Methotrexate	decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	affects expression	1
Cyclosporine	decreases expression	1
Cadmium Chloride	increases abundance, increases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00326833	PHASE4	UNKNOWN	How Many Patients Are in Need of Vitamin B12 Injections?
NCT02270749	PHASE4	COMPLETED	Vitamin Deficiencies and Suppletion in Morbid Obesity
NCT07029698	PHASE4	RECRUITING	A Study to See if a Combination of Vitamins That is Injected Into a Muscle is as Good and Safe as a Vitamin That is Taken by Mouth
NCT00279552	PHASE2	COMPLETED	Can Recombinant Human Intrinsic Factor Be Used for Evaluation of the Vitamin B12 Absorption?
NCT00699478	PHASE2	COMPLETED	Oral Vitamin B12 Administration for Vitamin B12 Deficiency After Total Gastrectomy
NCT05902351	Not specified	RECRUITING	Natural History Study for Charcot Marie Tooth Disease
NCT00467623	Not specified	COMPLETED	Holotranscobalamin Remains Unchanged During Pregnancy
NCT00826657	Not specified	COMPLETED	Vitamin B12 Supplementation Study
NCT00843453	Not specified	COMPLETED	Long-term Use of Proton Pump Inhibitors May Cause Vitamin B12 Deficiency in the Institutionalized Elderly
NCT01136512	Not specified	COMPLETED	Metformin Use and Vitamin B12 Deficiency
NCT01297361	Not specified	COMPLETED	The Association Between Religious Origin and Age, and Vitamin B12 and Folic Acid Plasma Levels in Non Jewish Population in Western Galilee
NCT01584050	Not specified	COMPLETED	Relative Bioavailability of Folic Acid and L-5-Methlytetrahydrofolate
NCT01661309	Not specified	COMPLETED	Supplementary Vitamin B12 Effects on Elevated Homocysteine Levels of Vegetarians - Clinical Trial
NCT01876329	Not specified	COMPLETED	Autoantibodies to Gastric Parietal Cells in Rheumatoid Arthritis Patients
NCT01876732	Not specified	COMPLETED	Impact of Vitamin B12 Replacement on Epogen Dosing and Improvement of Quality of Life in Hemodialysis Patients
NCT02076347	Not specified	COMPLETED	Comparison of Two Pharmacist-led Population Management Approaches to Increase Monitoring of Vitamin B12 and Serum Creatinine Levels for Patients on Metformin
NCT02540642	Not specified	COMPLETED	Effect of Vitamin B12 Supplementation on Glycaemic Control in Uncontrolled Hyperhomocysteinemic Type 2 Diabetic Patients
NCT02679833	Not specified	COMPLETED	Effect of Toothpaste Fortified With Cyanocobalamin on Vitamin B12 Status
NCT04048330	Not specified	UNKNOWN	Periconceptional Surveillance in India
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening
NCT06528366	Not specified	ACTIVE_NOT_RECRUITING	Heart Failure With Reduced Ejection Fraction: Adjuvant Therapy With Neurostimulation and Chlorella Pyrenoidosa (HD-tDCS)