FAM32A
gene geneOn this page
Also known as DKFZP586O0120OTAG-12
Summary
FAM32A (family with sequence similarity 32 member A, HGNC:24563) is a protein-coding gene on chromosome 19p13.11, encoding Protein FAM32A (Q9Y421). Isoform 1, but not isoform 2 or isoform 3, may induce G2 arrest and apoptosis. It is a selective cancer dependency (DepMap: 80.0% of cell lines).
Enables RNA binding activity. Predicted to be involved in apoptotic process. Located in nucleolus and nucleoplasm.
Source: NCBI Gene 26017 — RefSeq curated summary.
At a glance
- Clinical variants (ClinVar): 18 total
- Cancer dependency (DepMap): dependent in 80.0% of screened cell lines
- MANE Select transcript:
NM_014077
Identifiers
Gene identifiers
| Field | Value |
|---|---|
| HGNC ID | HGNC:24563 |
| Approved symbol | FAM32A |
| Name | family with sequence similarity 32 member A |
| Location | 19p13.11 |
| Locus type | gene with protein product |
| Status | Approved |
| Aliases | DKFZP586O0120, OTAG-12 |
| Ensembl gene | ENSG00000105058 |
| Ensembl biotype | protein_coding |
| OMIM | 614554 |
| Entrez | 26017 |
Gene structure
Transcript identifiers
Ensembl transcripts: 6 — 5 protein_coding, 1 nonsense_mediated_decay
ENST00000263384, ENST00000585831, ENST00000587351, ENST00000588367, ENST00000589852, ENST00000921004
RefSeq mRNA: 1 — MANE Select: NM_014077
NM_014077
CCDS: CCDS12341
Canonical transcript exons
ENST00000263384 — 4 exons
| Exon | Start | End |
|---|---|---|
| ENSE00000873431 | 16190887 | 16192046 |
| ENSE00001131027 | 16185624 | 16185765 |
| ENSE00002794630 | 16185410 | 16185516 |
| ENSE00003536196 | 16190520 | 16190573 |
Expression profiles
Bgee: expression breadth ubiquitous, 300 present calls, max score 97.51.
FANTOM5 (CAGE): breadth ubiquitous, TPM avg 114.6849 / max 1324.0698, expressed in 1826 samples.
FANTOM5 promoters (1 alternative TSS)
| Promoter ID | TPM avg | Samples expressed |
|---|---|---|
| 174389 | 114.6849 | 1826 |
Top tissues by expression
301 total, by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| cortical plate | UBERON:0005343 | 97.51 | gold quality |
| granulocyte | CL:0000094 | 97.18 | gold quality |
| monocyte | CL:0000576 | 96.90 | gold quality |
| leukocyte | CL:0000738 | 96.87 | gold quality |
| mononuclear cell | CL:0000842 | 96.87 | gold quality |
| ganglionic eminence | UBERON:0004023 | 96.74 | gold quality |
| mucosa of transverse colon | UBERON:0004991 | 96.42 | gold quality |
| gall bladder | UBERON:0002110 | 96.07 | gold quality |
| left coronary artery | UBERON:0001626 | 96.06 | gold quality |
| popliteal artery | UBERON:0002250 | 95.90 | gold quality |
| tibial artery | UBERON:0007610 | 95.89 | gold quality |
| descending thoracic aorta | UBERON:0002345 | 95.86 | gold quality |
| coronary artery | UBERON:0001621 | 95.84 | gold quality |
| right coronary artery | UBERON:0001625 | 95.82 | gold quality |
| muscle layer of sigmoid colon | UBERON:0035805 | 95.81 | gold quality |
| lower esophagus | UBERON:0013473 | 95.79 | gold quality |
| lower esophagus muscularis layer | UBERON:0035833 | 95.79 | gold quality |
| skin of leg | UBERON:0001511 | 95.75 | gold quality |
| right adrenal gland cortex | UBERON:0035827 | 95.73 | gold quality |
| aorta | UBERON:0000947 | 95.71 | gold quality |
| transverse colon | UBERON:0001157 | 95.71 | gold quality |
| body of stomach | UBERON:0001161 | 95.71 | gold quality |
| left adrenal gland | UBERON:0001234 | 95.68 | gold quality |
| left adrenal gland cortex | UBERON:0035825 | 95.58 | gold quality |
| right adrenal gland | UBERON:0001233 | 95.57 | gold quality |
| rectum | UBERON:0001052 | 95.56 | gold quality |
| small intestine Peyer’s patch | UBERON:0003454 | 95.52 | gold quality |
| thoracic aorta | UBERON:0001515 | 95.50 | gold quality |
| endometrium epithelium | UBERON:0004811 | 95.47 | gold quality |
| esophagogastric junction muscularis propria | UBERON:0035841 | 95.44 | gold quality |
Single-cell (SCXA)
Detected in 3 experiment(s), a significant marker in 1.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-ANND-3 | yes | 11.45 |
| E-MTAB-6386 | no | 382.16 |
| E-HCAD-31 | no | 2.53 |
Regulation
Is transcription factor: no
miRNA regulators (miRDB)
26 targeting FAM32A, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):
| miRNA | Max score | Avg score | miRNA target_count |
|---|---|---|---|
| HSA-MIR-8485 | 100.00 | 77.57 | 4731 |
| HSA-MIR-150-5P | 99.99 | 66.69 | 1976 |
| HSA-MIR-570-3P | 99.96 | 72.41 | 4910 |
| HSA-MIR-6768-5P | 99.92 | 67.36 | 1942 |
| HSA-MIR-4496 | 99.88 | 68.89 | 2236 |
| HSA-MIR-629-3P | 99.85 | 67.99 | 1875 |
| HSA-MIR-3180-5P | 99.82 | 69.12 | 2422 |
| HSA-MIR-4713-5P | 99.78 | 67.80 | 1794 |
| HSA-MIR-6885-3P | 99.75 | 70.36 | 3187 |
| HSA-MIR-3202 | 99.66 | 67.70 | 2737 |
| HSA-MIR-298 | 99.63 | 67.56 | 1916 |
| HSA-MIR-6722-3P | 99.45 | 67.62 | 1919 |
| HSA-MIR-3182 | 99.40 | 68.15 | 2454 |
| HSA-MIR-7160-5P | 99.11 | 67.17 | 2207 |
| HSA-MIR-1909-3P | 99.03 | 66.56 | 1662 |
| HSA-MIR-5001-3P | 98.91 | 67.28 | 1394 |
| HSA-MIR-421 | 98.90 | 67.04 | 1883 |
| HSA-MIR-4290 | 98.51 | 65.17 | 907 |
| HSA-MIR-4709-5P | 98.51 | 67.25 | 1335 |
| HSA-MIR-6870-3P | 98.08 | 65.10 | 692 |
| HSA-MIR-4669 | 97.94 | 62.71 | 224 |
| HSA-MIR-3650 | 97.88 | 64.89 | 693 |
| HSA-MIR-6501-5P | 97.41 | 68.24 | 712 |
| HSA-MIR-3137 | 97.26 | 66.78 | 761 |
| HSA-MIR-6815-5P | 96.05 | 65.55 | 662 |
| HSA-MIR-6865-5P | 96.05 | 65.58 | 675 |
Functional genomics
DepMap (CRISPR cell-line fitness): dependent in 80.0% of screened cell lines.
Literature-anchored findings (GeneRIF, showing 1)
- study showed that hOTAG-12b increases mRNAs of pro-apoptotic genes such as BAD, GADD45alpha and CIEDB, while inhibiting anti-apoptotic NAIP and Akt1 expression, suggesting that hOTAG-12b-induced apoptosis might be p53-independent (PMID:21339736)
Cross-species orthologs
6 orthologs
| Organism | Symbol | Gene ID |
|---|---|---|
| danio_rerio | fam32a | ENSDARG00000042660 |
| mus_musculus | Fam32a | ENSMUSG00000003039 |
| rattus_norvegicus | Fam32al1 | ENSRNOG00000015168 |
| rattus_norvegicus | Fam32a | ENSRNOG00000066630 |
| drosophila_melanogaster | CG15432 | FBGN0031603 |
| caenorhabditis_elegans | WBGENE00010479 |
Protein
Protein identifiers
Protein FAM32A — Q9Y421 (reviewed: Q9Y421)
Alternative names: Ovarian tumor-associated gene 12
All UniProt accessions (4): Q9Y421, K7EIY1, K7ELZ8, K7ENN5
UniProt curated annotations — full annotation on UniProt →
Function. Isoform 1, but not isoform 2 or isoform 3, may induce G2 arrest and apoptosis. May also increase cell sensitivity to apoptotic stimuli.
Subcellular location. Nucleus Nucleus.
Tissue specificity. Expressed in ovary, with isoform 1 being predominant.
Induction. By etoposide, puromycin or carboplatin.
Similarity. Belongs to the FAM32 family.
Isoforms (3)
| UniProt ID | Names | Canonical? |
|---|---|---|
| Q9Y421-1 | 1, OTAG-12b | yes |
| Q9Y421-2 | 2, OTAG-12a | |
| Q9Y421-3 | 3, OTAG-12c |
RefSeq proteins (1): NP_054796* (*=MANE)
Domains & families (InterPro)
| ID | Name | Type |
|---|---|---|
| IPR013865 | FAM32A | Family |
Pfam: PF08555
UniProt features (5 total): splice variant 2, chain 1, region of interest 1, compositionally biased region 1
Structure
Experimental structures (PDB)
5 structures.
| PDB | Method | Resolution (Å) |
|---|---|---|
| 8C6J | ELECTRON MICROSCOPY | 2.8 |
| 6QDV | ELECTRON MICROSCOPY | 3.3 |
| 9FMD | ELECTRON MICROSCOPY | 3.3 |
| 7W5A | ELECTRON MICROSCOPY | 3.6 |
| 7W5B | ELECTRON MICROSCOPY | 4.3 |
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-Q9Y421-F1 | 79.85 | 0.32 |
Function
Pathways and Gene Ontology
Reactome pathways
1 pathways
| ID | Pathway |
|---|---|
| R-HSA-72163 | mRNA Splicing - Major Pathway |
MSigDB gene sets: 121 (showing top):
GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, FOSTER_TOLERANT_MACROPHAGE_UP, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GOBP_RNA_SPLICING, REACTOME_MRNA_SPLICING, TIEN_INTESTINE_PROBIOTICS_24HR_UP, BREDEMEYER_RAG_SIGNALING_NOT_VIA_ATM_UP, REACTOME_METABOLISM_OF_RNA, GOCC_U2_TYPE_SPLICEOSOMAL_COMPLEX, GOCC_CATALYTIC_STEP_2_SPLICEOSOME, CHESLER_BRAIN_QTL_CIS, GOCC_SPLICEOSOMAL_COMPLEX
GO Biological Process (1): apoptotic process (GO:0006915)
GO Molecular Function (2): RNA binding (GO:0003723), protein binding (GO:0005515)
GO Cellular Component (3): nucleoplasm (GO:0005654), nucleolus (GO:0005730), nucleus (GO:0005634)
Reactome top-level categories
Rollup of top-1 pathways:
| Category | Pathways |
|---|---|
| mRNA Splicing | 1 |
GO top-level categories
Rollup of top GO terms by namespace:
| Category | Terms |
|---|---|
| nuclear lumen | 2 |
| programmed cell death | 1 |
| apoptotic signaling pathway | 1 |
| execution phase of apoptosis | 1 |
| nucleic acid binding | 1 |
| binding | 1 |
| cellular anatomical structure | 1 |
| intracellular membraneless organelle | 1 |
| intracellular membrane-bounded organelle | 1 |
Protein interactions and networks
STRING
530 interactions, top by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| FAM32A | PRKRIP1 | Q9H875 | 665 |
| FAM32A | CACTIN | Q8WUQ7 | 608 |
| FAM32A | SLU7 | O95391 | 604 |
| FAM32A | CCDC90B | Q9GZT6 | 592 |
| FAM32A | SDE2 | Q6IQ49 | 575 |
| FAM32A | RBM18 | Q96H35 | 541 |
| FAM32A | YJU2 | Q9BW85 | 516 |
| FAM32A | LRRC66 | Q68CR7 | 452 |
| FAM32A | SYF2 | O95926 | 444 |
| FAM32A | UBOX5 | O94941 | 443 |
| FAM32A | ZMAT2 | Q96NC0 | 437 |
| FAM32A | CFAP97 | Q9P2B7 | 427 |
| FAM32A | GLOD4 | Q9HC38 | 417 |
| FAM32A | KCTD10 | Q9H3F6 | 411 |
| FAM32A | ACTR10 | Q9NZ32 | 411 |
IntAct
28 interactions, top by confidence:
| A | B | Type | Score |
|---|---|---|---|
| CCDC60 | DCP1B | psi-mi:“MI:0914”(association) | 0.530 |
| RPL4 | TEFM | psi-mi:“MI:0914”(association) | 0.530 |
| CWC22 | FAM32A | psi-mi:“MI:0915”(physical association) | 0.510 |
| FAM32A | CWC22 | psi-mi:“MI:0915”(physical association) | 0.510 |
| CFTR | CNOT1 | psi-mi:“MI:0914”(association) | 0.480 |
| steC | SCD | psi-mi:“MI:0914”(association) | 0.460 |
| Ccdc12 | PLRG1 | psi-mi:“MI:0914”(association) | 0.350 |
| CCDC22 | VPS26C | psi-mi:“MI:0914”(association) | 0.350 |
| CCDC60 | ZNF593 | psi-mi:“MI:0914”(association) | 0.350 |
| CFTR | POTEF | psi-mi:“MI:0914”(association) | 0.350 |
| MAPT | SHTN1 | psi-mi:“MI:0914”(association) | 0.350 |
| MAGEA9 | CIBAR1 | psi-mi:“MI:0914”(association) | 0.350 |
| MRPL53 | psi-mi:“MI:0914”(association) | 0.350 | |
| MAGEA9 | MED19 | psi-mi:“MI:0914”(association) | 0.350 |
| DUSP22 | RAP2A | psi-mi:“MI:0914”(association) | 0.350 |
| GNLY | GTPBP10 | psi-mi:“MI:0914”(association) | 0.350 |
| PSRC1 | MPHOSPH10 | psi-mi:“MI:0914”(association) | 0.350 |
| RPL26L1 | ZNF316 | psi-mi:“MI:0914”(association) | 0.350 |
| RRP7A | MAGEB2 | psi-mi:“MI:0914”(association) | 0.350 |
| ZNF346 | ZNF316 | psi-mi:“MI:0914”(association) | 0.350 |
| NFIB | psi-mi:“MI:0914”(association) | 0.350 | |
| HRAS | IGKV2D-24 | psi-mi:“MI:0914”(association) | 0.350 |
| KRAS | psi-mi:“MI:0914”(association) | 0.350 | |
| HNRNPC | SBNO1 | psi-mi:“MI:2364”(proximity) | 0.270 |
| NPM1 | SBNO1 | psi-mi:“MI:2364”(proximity) | 0.270 |
| NSFL1C | FAM32A | psi-mi:“MI:0915”(physical association) | 0.000 |
BioGRID (40): FAM32A (Reconstituted Complex), FAM32A (Affinity Capture-MS), FAM32A (Affinity Capture-MS), FAM32A (Synthetic Lethality), FAM32A (Affinity Capture-MS), FAM32A (Affinity Capture-MS), FAM32A (Affinity Capture-MS), FAM32A (Proximity Label-MS), FAM32A (Proximity Label-MS), FAM32A (Proximity Label-MS), FAM32A (Proximity Label-MS), FAM32A (Proximity Label-MS), FAM32A (Proximity Label-MS), FAM32A (Affinity Capture-MS), FAM32A (Affinity Capture-MS)
ESM2 similar proteins: A0A089QKZ7, A1WW03, A4R1G4, A6QR31, A6RKG5, A7E4K0, A8HV31, A9GN39, B1LSP9, B1W0D5, B2RYG1, B6HGB5, B6K8A0, B8NDQ2, C4Z073, C9S8J9, G2TRK9, P11573, P46532, P52154, P52157, P55613, P64952, P66029, P79058, P9WHF2, P9WHF3, P9WLI4, P9WLI5, Q05190, Q08000, Q0V389, Q28C44, Q2U9C3, Q3LSS0, Q50229, Q58DU0, Q5M9I6, Q5R9E5, Q640E9
Diamond homologs: A6QR31, B0JZ89, B2RYG1, Q5R9E5, Q6GQN4, Q92363, Q9CR80, Q9Y421
SIGNOR signaling
0 interactions.
Disease & clinical
Clinical variants and AI predictions
ClinVar
18 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 0 |
| Likely pathogenic | 0 |
| Uncertain significance | 9 |
| Likely benign | 0 |
| Benign | 0 |
Top pathogenic / likely-pathogenic (0)
SpliceAI
562 predictions. Top by Δscore:
| Variant | Effect | Δscore |
|---|---|---|
| 19:16185503:G:GT | donor_gain | 1.0000 |
| 19:16185514:GCG:G | donor_gain | 1.0000 |
| 19:16185762:GCGG:G | donor_gain | 1.0000 |
| 19:16185763:CGGG:C | donor_loss | 1.0000 |
| 19:16185764:GG:G | donor_gain | 1.0000 |
| 19:16185764:GGGT:G | donor_loss | 1.0000 |
| 19:16185765:GG:G | donor_gain | 1.0000 |
| 19:16185765:GGT:G | donor_loss | 1.0000 |
| 19:16185766:G:GG | donor_gain | 1.0000 |
| 19:16185766:GTGA:G | donor_loss | 1.0000 |
| 19:16185767:T:G | donor_loss | 1.0000 |
| 19:16190515:TCCAG:T | acceptor_loss | 1.0000 |
| 19:16190517:CAG:C | acceptor_loss | 1.0000 |
| 19:16190518:A:AC | acceptor_loss | 1.0000 |
| 19:16190518:A:AG | acceptor_gain | 1.0000 |
| 19:16190519:G:GA | acceptor_gain | 1.0000 |
| 19:16190519:GC:G | acceptor_gain | 1.0000 |
| 19:16190519:GCA:G | acceptor_gain | 1.0000 |
| 19:16190519:GCAA:G | acceptor_gain | 1.0000 |
| 19:16190570:GGAG:G | donor_gain | 1.0000 |
| 19:16190571:GAG:G | donor_gain | 1.0000 |
| 19:16190571:GAGG:G | donor_gain | 1.0000 |
| 19:16190571:GAGGT:G | donor_loss | 1.0000 |
| 19:16190572:AGG:A | donor_loss | 1.0000 |
| 19:16190573:GGTG:G | donor_loss | 1.0000 |
| 19:16190574:G:GA | donor_loss | 1.0000 |
| 19:16190574:G:GG | donor_gain | 1.0000 |
| 19:16190575:T:A | donor_loss | 1.0000 |
| 19:16185516:GGTGA:G | donor_loss | 0.9900 |
| 19:16185517:G:GC | donor_loss | 0.9900 |
AlphaMissense
737 scored. Top likely-pathogenic:
| Variant | Protein change | am_pathogenicity |
|---|---|---|
| 19:16190556:C:G | H85D | 1.000 |
| 19:16190558:C:A | H85Q | 1.000 |
| 19:16190558:C:G | H85Q | 1.000 |
| 19:16190561:G:C | K86N | 1.000 |
| 19:16190561:G:T | K86N | 1.000 |
| 19:16190891:T:C | F92S | 1.000 |
| 19:16190895:C:A | N93K | 1.000 |
| 19:16190895:C:G | N93K | 1.000 |
| 19:16190903:T:A | L96Q | 1.000 |
| 19:16190903:T:C | L96P | 1.000 |
| 19:16190912:T:C | L99P | 1.000 |
| 19:16190920:C:G | H102D | 1.000 |
| 19:16190926:G:C | D104H | 1.000 |
| 19:16190927:A:C | D104A | 1.000 |
| 19:16190927:A:G | D104G | 1.000 |
| 19:16190927:A:T | D104V | 1.000 |
| 19:16190930:T:A | I105N | 1.000 |
| 19:16190930:T:C | I105T | 1.000 |
| 19:16190937:A:C | K107N | 1.000 |
| 19:16190937:A:T | K107N | 1.000 |
| 19:16190941:A:C | S109R | 1.000 |
| 19:16190943:C:A | S109R | 1.000 |
| 19:16190943:C:G | S109R | 1.000 |
| 19:16190944:T:A | W110R | 1.000 |
| 19:16190944:T:C | W110R | 1.000 |
| 19:16185731:C:A | A61D | 0.999 |
| 19:16185739:G:C | A64P | 0.999 |
| 19:16185742:T:C | F65L | 0.999 |
| 19:16185744:C:A | F65L | 0.999 |
| 19:16185744:C:G | F65L | 0.999 |
dbSNP variants (sampled 300 via entrez): RS1000025908 (19:16184018 C>G), RS1000028752 (19:16187286 C>G,T), RS1000059785 (19:16186989 G>A), RS1000480301 (19:16187989 A>C,G), RS1000949260 (19:16187415 A>G), RS1001085087 (19:16187584 G>A,T), RS1001848880 (19:16187784 T>C,G), RS1001922358 (19:16187593 C>T), RS1002168457 (19:16187698 G>C), RS1002503950 (19:16189311 C>T), RS1002640297 (19:16185261 C>G,T), RS1003748027 (19:16192114 G>A), RS1003779111 (19:16190677 G>A,C), RS1003865071 (19:16190581 G>A), RS1003938942 (19:16190263 C>T)
Disease associations
OMIM: gene MIM:614554 | disease phenotypes:
GenCC curated gene-disease
Mondo (0):
Orphanet (0):
HPO phenotypes
0 total (0 of 0 shown, HPO-id order):
GWAS associations
0 associations (top):
Drugs & pharmacology
Drug and pharmacology data
Is drug target: no
PharmGKB: 1 entry (VIP=true, CPIC=false)
CTD chemical–gene interactions
26 total (human), top 26 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| Tobacco Smoke Pollution | increases expression | 2 |
| bisphenol F | affects cotreatment, decreases expression | 1 |
| triphenyl phosphate | affects expression | 1 |
| beta-lapachone | decreases expression | 1 |
| sodium arsenite | increases expression | 1 |
| (4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II) | increases expression | 1 |
| 4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid | increases expression | 1 |
| Resveratrol | affects cotreatment, increases expression | 1 |
| Leflunomide | decreases expression | 1 |
| Atrazine | decreases expression | 1 |
| Benzo(a)pyrene | increases methylation | 1 |
| Copper | affects binding, decreases expression | 1 |
| Dexamethasone | affects cotreatment, decreases expression | 1 |
| Disulfiram | affects binding, decreases expression | 1 |
| Doxorubicin | increases expression | 1 |
| Indomethacin | decreases expression, affects cotreatment | 1 |
| Plant Extracts | affects cotreatment, increases expression | 1 |
| Selenium | increases expression | 1 |
| Smoke | decreases expression | 1 |
| Tetrachlorodibenzodioxin | increases expression | 1 |
| Tretinoin | increases expression | 1 |
| Valproic Acid | affects expression | 1 |
| 1-Methyl-3-isobutylxanthine | affects cotreatment, decreases expression | 1 |
| Cyclosporine | decreases expression | 1 |
| Copper Sulfate | increases expression | 1 |
| Lactic Acid | decreases expression | 1 |
Clinical trials (associated diseases)
0 trials via MONDO — disease-level, not drug-specific.
Related Atlas pages
No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.